The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment

Lei       Zhang; Mengyang       Wu; Ruicong       Su; Di       Zhang; Guilian       Yang
doi:10.2174/1574892816666211202154536
Abstract

Background: The ubiquitin-proteasome system (UPS) is critical in cellular protein degradation and widely involved in the regulations of cancer hallmarks. Targeting the UPS pathway has emerged as a promising novel treatment in hematological malignancies and solid tumors.
Objective: This review mainly focuses on the preclinical results of proteasome inhibitors in solid tumors.
Methods: We analyzed the published articles associated with the anticancer results of proteasome inhibitors alone or combination chemotherapy in solid tumors. Important data presented in abstract form were also discussed in this review.
Results/Conclusion: Proteasome inhibitors, such as bortezomib and carfilzomib, are highly effective in treating solid tumors. The anticancer efficacy is not limited to affect the proteasomal inhibition- associated signaling pathways but also widely involves the signaling pathways related to cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT). In addition, proteasome inhibitors overcome the conventional chemo-resistance of standard chemotherapeutics by inhibiting signaling pathways, such as NF-κB or PI3K/Akt. Combination chemotherapy of proteasome inhibitors and standard chemotherapeutics are widely investigated in multiple relapsed or chemo-resistant solid tumor types, such as breast cancer and pancreatic cancer. The proteasome inhibitors re-sensitize the standard chemotherapeutic regimens and induce synergistic anticancer effects. The development of novel proteasome inhibitors and delivery systems also improves the proteasome inhibitors’ anticancer efficacy in solid tumors. This review summarizes the current preclinical results of proteasome inhibitors in solid tumors and reveals the potential anticancer mechanisms.
Keywords: Proteasome, proteasome inhibitors, bortezomib, solid tumor, cell cycle, apoptosis, metastasis, angiogenesis, combination chemotherapy.
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[1] 
Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol  2017; 14(7): 417-33.
[http://dx.doi.org/10.1038/nrclinonc.2016.206] [PMID: 28117417] 
[2] 
Chen L, Madura K. Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Cancer Res  2005; 65(13): 5599-606.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0201] [PMID: 15994932] 
[3] 
Bazzaro M, Lee MK, Zoso A, et al. Ubiquitin-proteasome system stress sensitizes ovarian cancer to proteasome inhibitor-induced apoptosis. Cancer Res  2006; 66(7): 3754-63.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2321] [PMID: 16585202] 
[4] 
Aichinger C, Schreier P, Ebbert R, Huber R, Groll M. InventorsMethods for identifuing inhibitors of the 20S and 26S proteasome. Patent US 20040053312, 2004.
[5] 
Song JE, Lee L, Ban E, Kim EE, Yoo YS. InventorsRapid method to analyze ubiquitin-proteasome activity and to screen for ubiquitin-proteasome inhibitor. Patent US 20150362480, 2015.
[6] 
Vaddi GR, Stein RL, Dick LR, Palombella VJ, Lightcap ES. InventorsMethod for monitoring proteasome inhibitor drug action 1999.
[7] 
Johnson DE. The ubiquitin-proteasome system: opportunities for therapeutic intervention in solid tumors. Endocr Relat Cancer  2015; 22(1): T1-T17.
[http://dx.doi.org/10.1530/ERC-14-0005] [PMID: 24659480] 
[8] 
Deckert J, Lejeune P, Mayo M, Park PU. InventorsAntitumors combinations containing antibodies recognizing specifically CD38 and Bortezomib. Patent US 20140186337, 2014.
[9] 
Choi KS, Kim IY, Yoon MJ, Lee AR. InventorsPharmaceutical composition for preventing or treating cancer, containg proteasome inhibitor and loperamide as active ingredients. US 20160324843, 2016.
[10] 
Huang Z, Wu Y, Zhou X, et al. Efficacy of therapy with bortezomib in solid tumors: a review based on 32 clinical trials. Future Oncol  2014; 10(10): 1795-807.
[http://dx.doi.org/10.2217/fon.14.30] [PMID: 25303058] 
[11] 
Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci USA  1999; 96(20): 11364-9.
[http://dx.doi.org/10.1073/pnas.96.20.11364] [PMID: 10500182] 
[12] 
Gupta I, Singh K, Varshney NK, Khan S. Delineating crosstalk mechanisms of the ubiquitin proteasome system that regulate apoptosis. Front Cell Dev Biol  2018; 6: 11.
[http://dx.doi.org/10.3389/fcell.2018.00011] [PMID: 29479529] 
[13] 
Roeten MSF, Cloos J, Jansen G. Positioning of proteasome inhibitors in therapy of solid malignancies. Cancer Chemother Pharmacol  2018; 81(2): 227-43.
[http://dx.doi.org/10.1007/s00280-017-3489-0] [PMID: 29184971] 
[14] 
Reits E, Griekspoor A, Neijssen J, et al. Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I. Immunity  2003; 18(1): 97-108.
[http://dx.doi.org/10.1016/S1074-7613(02)00511-3] [PMID: 12530979] 
[15] 
Hitzerd SM, Verbrugge SE, Ossenkoppele G, Jansen G, Peters GJ. Positioning of aminopeptidase inhibitors in next generation cancer therapy. Amino Acids  2014; 46(4): 793-808.
[http://dx.doi.org/10.1007/s00726-013-1648-0] [PMID: 24385243] 
[16] 
Komander D, Clague MJ, Urbé S. Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol  2009; 10(8): 550-63.
[http://dx.doi.org/10.1038/nrm2731] [PMID: 19626045] 
[17] 
Park J, Cho J, Song EJ. Ubiquitin-proteasome system (UPS) as a target for anticancer treatment. Arch Pharm Res  2020; 43(11): 1144-61.
[http://dx.doi.org/10.1007/s12272-020-01281-8] [PMID: 33165832] 
[18] 
Rojkjaer B, Endell W. InventorsMethod for the treatment of multiple myeloma or non-Hodgkins lymphoma with anti-CD38 antibody and bortezomib or carfilzomib. US 20180022823, 2018.
[19] 
Kuhn DJ, Chen Q, Voorhees PM, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood  2007; 110(9): 3281-90.
[http://dx.doi.org/10.1182/blood-2007-01-065888] [PMID: 17591945] 
[20] 
Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res  2010; 70(5): 1970-80.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2766] [PMID: 20160034] 
[21] 
Chauhan D, Tian Z, Zhou B, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res  2011; 17(16): 5311-21.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0476] [PMID: 21724551] 
[22] 
Teicher BA, Tomaszewski JE. Proteasome inhibitors. Biochem Pharmacol  2015; 96(1): 1-9.
[http://dx.doi.org/10.1016/j.bcp.2015.04.008] [PMID: 25935605] 
[23] 
Hurchla MA, Garcia-Gomez A, Hornick MC, et al. The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects. Leukemia  2013; 27(2): 430-40.
[http://dx.doi.org/10.1038/leu.2012.183] [PMID: 22763387] 
[24] 
Ghobrial IM, Vij R, Siegel D, et al. A Phase Ib/II study of oprozomib in patients with advanced multiple myeloma and waldenström macroglobulinemia. Clin Cancer Res  2019; 25(16): 4907-16.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-3728] [PMID: 31142508] 
[25] 
Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif  2003; 36(3): 131-49.
[http://dx.doi.org/10.1046/j.1365-2184.2003.00266.x] [PMID: 12814430] 
[26] 
Wu WK, Cho CH, Lee CW, et al. Macroautophagy and ERK phosphorylation counteract the antiproliferative effect of proteasome inhibitor in gastric cancer cells. Autophagy  2010; 6(2): 228-38.
[http://dx.doi.org/10.4161/auto.6.2.11042] [PMID: 20087064] 
[27] 
Hong YS, Hong SW, Kim SM, et al. Bortezomib induces G2-M arrest in human colon cancer cells through ROS-inducible phosphorylation of ATM-CHK1. Int J Oncol  2012; 41(1): 76-82.
[PMID: 22552540] 
[28] 
Ikezoe T, Yang Y, Saito T, Koeffler HP, Taguchi H. Proteasome inhibitor PS-341 down-regulates prostate-specific antigen (PSA) and induces growth arrest and apoptosis of androgen-dependent human prostate cancer LNCaP cells. Cancer Sci  2004; 95(3): 271-5.
[http://dx.doi.org/10.1111/j.1349-7006.2004.tb02215.x] [PMID: 15016328] 
[29] 
Lu G, Punj V, Chaudhary PM. Proteasome inhibitor Bortezomib induces cell cycle arrest and apoptosis in cell lines derived from Ewing’s sarcoma family of tumors and synergizes with TRAIL. Cancer Biol Ther  2008; 7(4): 603-8.
[http://dx.doi.org/10.4161/cbt.7.4.5564] [PMID: 18223318] 
[30] 
Zhou Y, Wang K, Zhen S, Wang R, Luo W. Carfilzomib induces G2/M cell cycle arrest in human endometrial cancer cells via upregulation of p21Waf1/Cip1 and p27Kip1. Taiwan J Obstet Gynecol  2016; 55(6): 847-51.
[http://dx.doi.org/10.1016/j.tjog.2016.09.003] [PMID: 28040131] 
[31] 
Augello G, Modica M, Azzolina A, et al. Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells. Cell Death Dis  2018; 9(2): 28.
[http://dx.doi.org/10.1038/s41419-017-0195-0] [PMID: 29348495] 
[32] 
Yin D, Zhou H, Kumagai T, et al. Proteasome inhibitor PS-341 causes cell growth arrest and apoptosis in human glioblastoma multiforme (GBM). Oncogene  2005; 24(3): 344-54.
[http://dx.doi.org/10.1038/sj.onc.1208225] [PMID: 15531918] 
[33] 
Vaziri SA, Grabowski DR, Hill J, et al. Inhibition of proteasome activity by bortezomib in renal cancer cells is p53 dependent and VHL independent. Anticancer Res  2009; 29(8): 2961-9.
[PMID: 19661301] 
[34] 
Xue B, Huang W, Yuan X, et al. YSY01A, a novel proteasome inhibitor, induces cell cycle arrest on G2 phase in MCF-7 Cells via ERα and PI3K/Akt pathways. J Cancer  2015; 6(4): 319-26.
[http://dx.doi.org/10.7150/jca.10733] [PMID: 25767601] 
[35] 
Yang Y, Ikezoe T, Saito T, Kobayashi M, Koeffler HP, Taguchi H. Proteasome inhibitor PS-341 induces growth arrest and apoptosis of non-small cell lung cancer cells via the JNK/c-Jun/AP-1 signaling. Cancer Sci  2004; 95(2): 176-80.
[http://dx.doi.org/10.1111/j.1349-7006.2004.tb03200.x] [PMID: 14965369] 
[36] 
Williams SA, McConkey DJ. The proteasome inhibitor bortezomib stabilizes a novel active form of p53 in human LNCaP-Pro5 prostate cancer cells. Cancer Res  2003; 63(21): 7338-44.
[PMID: 14612532] 
[37] 
Ling YH, Liebes L, Jiang JD, et al. Mechanisms of proteasome inhibitor PS-341-induced G(2)-M-phase arrest and apoptosis in human non-small cell lung cancer cell lines. Clin Cancer Res  2003; 9(3): 1145-54.
[PMID: 12631620] 
[38] 
Li B, Dou QP. Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci USA  2000; 97(8): 3850-5.
[http://dx.doi.org/10.1073/pnas.070047997] [PMID: 10725400] 
[39] 
Nikrad M, Johnson T, Puthalalath H, Coultas L, Adams J, Kraft AS. The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Mol Cancer Ther  2005; 4(3): 443-9.
[http://dx.doi.org/10.1158/1535-7163.MCT-04-0260] [PMID: 15767553] 
[40] 
Ding WX, Ni HM, Chen X, Yu J, Zhang L, Yin XM. A coordinated action of Bax, PUMA, and p53 promotes MG132-induced mitochondria activation and apoptosis in colon cancer cells. Mol Cancer Ther  2007; 6(3): 1062-9.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0541] [PMID: 17363499] 
[41] 
Mortenson MM, Schlieman MG, Virudachalam S, et al. Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer. Lung Cancer  2005; 49(2): 163-70.
[http://dx.doi.org/10.1016/j.lungcan.2005.01.006] [PMID: 16022909] 
[42] 
Liu R, Fu C, Sun J, Wang X, Geng S, Wang X. A new perspective for osteosarcoma therapy: proteasome inhibition by MLN9708/2238 successfully induces apoptosis and cell cycle arrest and attenuates the invasion ability of osteosarcoma cells in vitro. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology  2017; 41(2): 451-65.
[43] 
Han B, Yao W, Oh YT, et al. The novel proteasome inhibitor carfilzomib activates and enhances extrinsic apoptosis involving stabilization of death receptor 5. Oncotarget  2015; 6(19): 17532-42.
[http://dx.doi.org/10.18632/oncotarget.3947] [PMID: 26009898] 
[44] 
He Q, Huang Y, Sheikh MS. Proteasome inhibitor MG132 upregulates death receptor 5 and cooperates with Apo2L/TRAIL to induce apoptosis in Bax-proficient and -deficient cells. Oncogene  2004; 23(14): 2554-8.
[http://dx.doi.org/10.1038/sj.onc.1207351] [PMID: 14691451] 
[45] 
Kiliccioglu I, Konac E, Varol N, Gurocak S, Yucel Bilen C. Apoptotic effects of proteasome and histone deacetylase inhibitors in prostate cancer cell lines. Genet Mol Res  2014; 13(2): 3721-31.
[http://dx.doi.org/10.4238/2014.May.9.17] [PMID: 24854658] 
[46] 
Vyas D, Lopez-Hisijos N, Shah P, et al. A second-generation proteasome inhibitor and doxorubicin modulates IL-6, pSTAT-3 and NF-kB Activity in MDA-MB-231 breast cancer cells. J Nanosci Nanotechnol  2017; 17(1): 175-85.
[http://dx.doi.org/10.1166/jnn.2017.12427] [PMID: 29617099] 
[47] 
Vandewynckel YP, Coucke C, Laukens D, et al. Next-generation proteasome inhibitor oprozomib synergizes with modulators of the unfolded protein response to suppress hepatocellular carcinoma. Oncotarget  2016; 7(23): 34988-5000.
[http://dx.doi.org/10.18632/oncotarget.9222] [PMID: 27167000] 
[48] 
Vandewynckel YP, Laukens D, Geerts A, et al. The paradox of the unfolded protein response in cancer. Anticancer Res  2013; 33(11): 4683-94.
[PMID: 24222102] 
[49] 
Bao W, Gu Y, Ta L, Wang K, Xu Z. Induction of autophagy by the MG-132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF-7 cells. Mol Med Rep  2016; 13(1): 796-804.
[http://dx.doi.org/10.3892/mmr.2015.4599] [PMID: 26648402] 
[50] 
Fribley A, Zeng Q, Wang CY. Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Mol Cell Biol  2004; 24(22): 9695-704.
[http://dx.doi.org/10.1128/MCB.24.22.9695-9704.2004] [PMID: 15509775] 
[51] 
Vaeteewoottacharn K, Kariya R, Matsuda K, et al. Perturbation of proteasome function by bortezomib leading to ER stress-induced apoptotic cell death in cholangiocarcinoma. J Cancer Res Clin Oncol  2013; 139(9): 1551-62.
[http://dx.doi.org/10.1007/s00432-013-1473-6] [PMID: 23877657] 
[52] 
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell  2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230] 
[53] 
Voutsadakis IA. The ubiquitin-proteasome system and signal transduction pathways regulating Epithelial Mesenchymal transition of cancer. J Biomed Sci  2012; 19: 67.
[http://dx.doi.org/10.1186/1423-0127-19-67] [PMID: 22827778] 
[54] 
Imamura T, Oshima Y, Hikita A. Regulation of TGF-β family signalling by ubiquitination and deubiquitination. J Biochem  2013; 154(6): 481-9.
[http://dx.doi.org/10.1093/jb/mvt097] [PMID: 24165200] 
[55] 
Bao X, Ren T, Huang Y, et al. Bortezomib induces apoptosis and suppresses cell growth and metastasis by inactivation of Stat3 signaling in chondrosarcoma. Int J Oncol  2017; 50(2): 477-86.
[http://dx.doi.org/10.3892/ijo.2016.3806] [PMID: 28000897] 
[56] 
Wang Z, Wang J, Li X, et al. Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1, Smurf1 and Smurf2. Int J Oncol  2014; 45(4): 1469-78.
[http://dx.doi.org/10.3892/ijo.2014.2545] [PMID: 25051198] 
[57] 
Baritaki S, Chapman A, Yeung K, Spandidos DA, Palladino M, Bonavida B. Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction. Oncogene  2009; 28(40): 3573-85.
[http://dx.doi.org/10.1038/onc.2009.214] [PMID: 19633685] 
[58] 
Raninga PV, Lee A, Sinha D, et al. Marizomib suppresses triple-negative breast cancer via proteasome and oxidative phosphorylation inhibition. Theranostics  2020; 10(12): 5259-75.
[http://dx.doi.org/10.7150/thno.42705] [PMID: 32373211] 
[59] 
Harris MA, Miles MA, Shekhar TM, et al. The proteasome inhibitor ixazomib inhibits the formation and growth of pulmonary and abdominal osteosarcoma metastases in mice. Cancers (Basel)  2020; 12(5): E1207.
[http://dx.doi.org/10.3390/cancers12051207] [PMID: 32403415] 
[60] 
Williamson MJ, Silva MD, Terkelsen J, et al. The relationship among tumor architecture, pharmacokinetics, pharmacodynamics, and efficacy of bortezomib in mouse xenograft models. Mol Cancer Ther  2009; 8(12): 3234-43.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0239] [PMID: 19934276] 
[61] 
Zhang L, Teng Y, Zhang Y, et al. Proteasome inhibitor bortezomib (PS-341) enhances RANKL-induced MDA-MB-231 breast cancer cell migration. Mol Med Rep  2012; 5(2): 580-4.
[PMID: 22101248] 
[62] 
Shahneh FZ, Baradaran B, Zamani F, Aghebati-Maleki L. Tumor angiogenesis and anti-angiogenic therapies. Hum Antibodies  2013; 22(1-2): 15-9.
[http://dx.doi.org/10.3233/HAB-130267] [PMID: 24284305] 
[63] 
Kim C, Kasuya J, Jeon J, Chung S, Kamm RD. A quantitative microfluidic angiogenesis screen for studying anti-angiogenic therapeutic drugs. Lab Chip  2015; 15(1): 301-10.
[http://dx.doi.org/10.1039/C4LC00866A] [PMID: 25370780] 
[64] 
Matsuo Y, Sawai H, Ochi N, et al. Proteasome inhibitor MG132 inhibits angiogenesis in pancreatic cancer by blocking NF-kappaB activity. Dig Dis Sci  2010; 55(4): 1167-76.
[http://dx.doi.org/10.1007/s10620-009-0814-4] [PMID: 19399612] 
[65] 
Sunwoo JB, Chen Z, Dong G, et al. Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clin Cancer Res  2001; 7(5): 1419-28.
[PMID: 11350913] 
[66] 
Nawrocki ST, Bruns CJ, Harbison MT, et al. Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther  2002; 1(14): 1243-53.
[PMID: 12516957] 
[67] 
Veschini L, Belloni D, Foglieni C, et al. Hypoxia-inducible transcription factor-1 alpha determines sensitivity of endothelial cells to the proteosome inhibitor bortezomib. Blood  2007; 109(6): 2565-70.
[http://dx.doi.org/10.1182/blood-2006-06-032664] [PMID: 17110461] 
[68] 
Bota DA, Alexandru D, Keir ST, Bigner D, Vredenburgh J, Friedman HS. Proteasome inhibition with bortezomib induces cell death in GBM stem-like cells and temozolomide-resistant glioma cell lines, but stimulates GBM stem-like cells’ VEGF production and angiogenesis. J Neurosurg  2013; 119(6): 1415-23.
[http://dx.doi.org/10.3171/2013.7.JNS1323] [PMID: 24093630] 
[69] 
Kern J, Untergasser G, Zenzmaier C, et al. GRP-78 secreted by tumor cells blocks the antiangiogenic activity of bortezomib. Blood  2009; 114(18): 3960-7.
[http://dx.doi.org/10.1182/blood-2009-03-209668] [PMID: 19713465] 
[70] 
Williams S, Pettaway C, Song R, Papandreou C, Logothetis C, McConkey DJ. Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts. Mol Cancer Ther  2003; 2(9): 835-43.
[PMID: 14555702] 
[71] 
Waks AG, Winer EP. Breast Cancer Treatment: A Review. JAMA  2019; 321(3): 288-300.
[http://dx.doi.org/10.1001/jama.2018.19323] [PMID: 30667505] 
[72] 
Lun M, Zhang PL, Siegelmann-Danieli N, Blasick TM, Brown RE. Intracellular inhibitory effects of Velcade correlate with morphoproteomic expression of phosphorylated-nuclear factor-kappaB and p53 in breast cancer cell lines. Ann Clin Lab Sci  2005; 35(1): 15-24.
[PMID: 15830705] 
[73] 
Wang Y, Rishi AK, Puliyappadamba VT, et al. Targeted proteasome inhibition by Velcade induces apoptosis in human mesothelioma and breast cancer cell lines. Cancer Chemother Pharmacol  2010; 66(3): 455-66.
[http://dx.doi.org/10.1007/s00280-009-1181-8] [PMID: 19960346] 
[74] 
Jones MD, Liu JC, Barthel TK, et al. A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes. Clin Cancer Res  2010; 16(20): 4978-89.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-3293] [PMID: 20843837] 
[75] 
Wang H, Yu Y, Jiang Z, et al. Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis. Sci Rep  2016; 6: 26456.
[http://dx.doi.org/10.1038/srep26456] [PMID: 27217076] 
[76] 
Shi Y, Yu Y, Wang Z, et al. Second-generation proteasome inhibitor carfilzomib enhances doxorubicin-induced cytotoxicity and apoptosis in breast cancer cells. Oncotarget  2016; 7(45): 73697-710.
[http://dx.doi.org/10.18632/oncotarget.12048] [PMID: 27655642] 
[77] 
Thaler S, Schmidt M, Roβwag S, Thiede G, Schad A, Sleeman JP. Proteasome inhibitors prevent bi-directional HER2/estrogen-receptor cross-talk leading to cell death in endocrine and lapatinib-resistant HER2+/ER+ breast cancer cells. Oncotarget  2017; 8(42): 72281-301.
[http://dx.doi.org/10.18632/oncotarget.20261] [PMID: 29069787] 
[78] 
Powers GL, Ellison-Zelski SJ, Casa AJ, Lee AV, Alarid ET. Proteasome inhibition represses ERalpha gene expression in ER+ cells: a new link between proteasome activity and estrogen signaling in breast cancer. Oncogene  2010; 29(10): 1509-18.
[http://dx.doi.org/10.1038/onc.2009.434] [PMID: 19946334] 
[79] 
Tseng LM, Liu CY, Chang KC, Chu PY, Shiau CW, Chen KF. CIP2A is a target of bortezomib in human triple negative breast cancer cells. Breast Cancer Res  2012; 14(2): R68.
[http://dx.doi.org/10.1186/bcr3175] [PMID: 22537901] 
[80] 
Uddin MM, Zou Y, Sharma T, Gatla HR, Vancurova I. Proteasome inhibition induces IKK-dependent interleukin-8 expression in triple negative breast cancer cells: Opportunity for combination therapy. PLoS One  2018; 13(8): e0201858.
[http://dx.doi.org/10.1371/journal.pone.0201858] [PMID: 30089134] 
[81] 
Fujita T, Doihara H, Washio K, et al. Proteasome inhibitor bortezomib increases PTEN expression and enhances trastuzumab-induced growth inhibition in trastuzumab-resistant cells. Anticancer Drugs  2006; 17(4): 455-62.
[http://dx.doi.org/10.1097/01.cad.0000198910.90819.06] [PMID: 16550004] 
[82] 
Thaler S, Thiede G, Hengstler JG, Schad A, Schmidt M, Sleeman JP. The proteasome inhibitor Bortezomib (Velcade) as potential inhibitor of estrogen receptor-positive breast cancer. International journal of cancer  2015; 137(3): 686-97.
[83] 
Adwal A, Kalita-de Croft P, Shakya R, et al. Tradeoff between metabolic i-proteasome addiction and immune evasion in triple-negative breast cancer. Life Sci Alliance  2020; 3(7): e201900562.
[http://dx.doi.org/10.26508/lsa.201900562] [PMID: 32423906] 
[84] 
Choi YH. Proteasome-mediated degradation of BRCA1 protein in MCF-7 human breast cancer cells. Int J Oncol  2001; 19(4): 687-93.
[http://dx.doi.org/10.3892/ijo.19.4.687] [PMID: 11562742] 
[85] 
Deshmukh RR, Kim S, Elghoul Y, Dou QP. P-glycoprotein inhibition sensitizes human breast cancer cells to proteasome inhibitors. J Cell Biochem  2017; 118(5): 1239-48.
[http://dx.doi.org/10.1002/jcb.25783] [PMID: 27813130] 
[86] 
Cardoso F, Durbecq V, Laes JF, et al. Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2- positive breast cancer cells in a synergistic manner. Mol Cancer Ther  2006; 5(12): 3042-51.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0104] [PMID: 17148762] 
[87] 
Hernández-Vargas H, von Kobbe C, Sánchez-Estévez C, Julián- Tendero M, Palacios J, Moreno-Bueno G. Inhibition of paclitaxel-induced proteasome activation influences paclitaxel cytotoxicity in breast cancer cells in a sequence-dependent manner. Cell Cycle  2007; 6(21): 2662-8.
[http://dx.doi.org/10.4161/cc.6.21.4821] [PMID: 17912036] 
[88] 
Domingo-Domènech J, Pippa R, Tápia M, Gascón P, Bachs O, Bosch M. Inactivation of NF-kappaB by proteasome inhibition contributes to increased apoptosis induced by histone deacetylase inhibitors in human breast cancer cells. Breast Cancer Res Treat  2008; 112(1): 53-62.
[http://dx.doi.org/10.1007/s10549-007-9837-8] [PMID: 18064564] 
[89] 
Shi YY, Small GW, Orlowski RZ. Proteasome inhibitors induce a p38 mitogen-activated protein kinase (MAPK)-dependent anti-apoptotic program involving MAPK phosphatase-1 and Akt in models of breast cancer. Breast Cancer Res Treat  2006; 100(1): 33-47.
[http://dx.doi.org/10.1007/s10549-006-9232-x] [PMID: 16807678] 
[90] 
Chang HY, Huang TC, Chen NN, Huang HC, Juan HF. Combination therapy targeting ectopic ATP synthase and 26S proteasome induces ER stress in breast cancer cells. Cell Death Dis  2014; 5: e1540.
[http://dx.doi.org/10.1038/cddis.2014.504] [PMID: 25429617] 
[91] 
Weyburne ES, Wilkins OM, Sha Z, et al. Inhibition of the proteasome β2 Site sensitizes triple-negative breast cancer cells to β5 inhibitors and suppresses Nrf1 activation. Cell Chem Biol  2017; 24(2): 218-30.
[http://dx.doi.org/10.1016/j.chembiol.2016.12.016] [PMID: 28132893] 
[92] 
Yao F, Wang G, Wei W, Tu Y, Tong H, Sun S. An autophagy inhibitor enhances the inhibition of cell proliferation induced by a proteasome inhibitor in MCF-7 cells. Mol Med Rep  2012; 5(1): 84-8.
[PMID: 21931937] 
[93] 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin  2020; 70(1): 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902] 
[94] 
Nijhawan D, Zack TI, Ren Y, et al. Cancer vulnerabilities unveiled by genomic loss. Cell  2012; 150(4): 842-54.
[http://dx.doi.org/10.1016/j.cell.2012.07.023] [PMID: 22901813] 
[95] 
Steinmetz R, Wagoner HA, Zeng P, et al. Mechanisms regulating the constitutive activation of the extracellular signal-regulated kinase (ERK) signaling pathway in ovarian cancer and the effect of ribonucleic acid interference for ERK1/2 on cancer cell proliferation. Mol Endocrinol  2004; 18(10): 2570-82.
[http://dx.doi.org/10.1210/me.2004-0082] [PMID: 15243131] 
[96] 
Tenev T, Marani M, McNeish I, Lemoine NR. Pro-caspase-3 overexpression sensitises ovarian cancer cells to proteasome inhibitors. Cell Death Differ  2001; 8(3): 256-64.
[http://dx.doi.org/10.1038/sj.cdd.4400808] [PMID: 11319608] 
[97] 
Kao C, Chao A, Tsai CL, et al. Phosphorylation of signal transducer and activator of transcription 1 reduces bortezomib-mediated apoptosis in cancer cells. Cell Death Dis  2013; 4: e512.
[http://dx.doi.org/10.1038/cddis.2013.38] [PMID: 23449448] 
[98] 
Zhu H, Zhang L, Dong F, et al. Bik/NBK accumulation correlates with apoptosis-induction by bortezomib (PS-341, Velcade) and other proteasome inhibitors. Oncogene  2005; 24(31): 4993-9.
[http://dx.doi.org/10.1038/sj.onc.1208683] [PMID: 15824729] 
[99] 
Zhou W, Hu J, Tang H, et al. Small interfering RNA targeting mcl-1 enhances proteasome inhibitor-induced apoptosis in various solid malignant tumors. BMC Cancer  2011; 11: 485.
[http://dx.doi.org/10.1186/1471-2407-11-485] [PMID: 22078414] 
[100] 
Al-Eisawi Z, Beale P, Chan C, Yu JQ, Huq F. Modulation of cisplatin cytotoxicity due to its combination with bortezomib and the nature of its administration. Anticancer Res  2011; 31(9): 2757-62.
[PMID: 21868517] 
[101] 
Al-Eisawi Z, Beale P, Chan C, Yu JQ, Huq F. Carboplatin and oxaliplatin in sequenced combination with bortezomib in ovarian tumour models. J Ovarian Res  2013; 6(1): 78.
[http://dx.doi.org/10.1186/1757-2215-6-78] [PMID: 24209693] 
[102] 
Pasquini L, Petronelli A, Petrucci E, et al. Primary ovarian cancer cells are sensitive to the proaptotic effects of proteasome inhibitors. Int J Oncol  2010; 36(3): 707-13.
[PMID: 20126991] 
[103] 
Bazzaro M, Lin Z, Santillan A, et al. Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor. Clin Cancer Res  2008; 14(22): 7340-7.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0642] [PMID: 19010849] 
[104] 
Zhang L, Hapon MB, Goyeneche AA, et al. Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors. Mol Oncol  2016; 10(7): 1099-117.
[http://dx.doi.org/10.1016/j.molonc.2016.05.001] [PMID: 27233943] 
[105] 
Taylor-Harding B, Agadjanian H, Nassanian H, et al. Indole-3- carbinol synergistically sensitises ovarian cancer cells to bortezomib treatment. Br J Cancer  2012; 106(2): 333-43.
[http://dx.doi.org/10.1038/bjc.2011.546] [PMID: 22166800] 
[106] 
Kuroda K, Liu H. The proteasome inhibitor, bortezomib, induces prostate cancer cell death by suppressing the expression of prostate-specific membrane antigen, as well as androgen receptor. Int J Oncol  2019; 54(4): 1357-66.
[http://dx.doi.org/10.3892/ijo.2019.4706] [PMID: 30720063] 
[107] 
Lin HK, Altuwaijri S, Lin WJ, Kan PY, Collins LL, Chang C. Proteasome activity is required for androgen receptor transcriptional activity via regulation of androgen receptor nuclear translocation and interaction with coregulators in prostate cancer cells. J Biol Chem  2002; 277(39): 36570-6.
[http://dx.doi.org/10.1074/jbc.M204751200] [PMID: 12119296] 
[108] 
Yemelyanov A, Bhalla P, Yang X, et al. Differential targeting of androgen and glucocorticoid receptors induces ER stress and apoptosis in prostate cancer cells: a novel therapeutic modality. Cell Cycle  2012; 11(2): 395-406.
[http://dx.doi.org/10.4161/cc.11.2.18945] [PMID: 22223138] 
[109] 
Fu Z, Lu C, Zhang C, Qiao B. PSMA5 promotes the tumorigenic process of prostate cancer and is related to bortezomib resistance. Anticancer Drugs  2019; 30(7): e0773.
[PMID: 30807553] 
[110] 
Goktas S, Baran Y, Ural AU, et al. Proteasome inhibitor bortezomib increases radiation sensitivity in androgen independent human prostate cancer cells. Urology  2010; 75(4): 793-8.
[http://dx.doi.org/10.1016/j.urology.2009.07.1215] [PMID: 19800672] 
[111] 
An J, Sun YP, Adams J, Fisher M, Belldegrun A, Rettig MB. Drug interactions between the proteasome inhibitor bortezomib and cytotoxic chemotherapy, tumor necrosis factor (TNF) alpha, and TNF-related apoptosis-inducing ligand in prostate cancer. Clin Cancer Res  2003; 9(12): 4537-45.
[PMID: 14555528] 
[112] 
Aras B, Yerlikaya A. Bortezomib and etoposide combinations exert synergistic effects on the human prostate cancer cell line PC-3. Oncol Lett  2016; 11(5): 3179-84.
[http://dx.doi.org/10.3892/ol.2016.4340] [PMID: 27123085] 
[113] 
Zhu H, Wang T, Xin Z, et al. An oral second-generation proteasome inhibitor oprozomib significantly inhibits lung cancer in a p53 independent manner in vitro. Acta Biochim Biophys Sin (Shanghai)  2019; 51(10): 1034-40.
[http://dx.doi.org/10.1093/abbs/gmz093] [PMID: 31518420] 
[114] 
Chattopadhyay N, Berger AJ, Koenig E, et al. KRAS genotype correlates with proteasome inhibitor ixazomib activity in preclinical in vivo models of colon and non-small cell lung cancer: Potential role of tumor metabolism. PLoS One  2015; 10(12): e0144825.
[http://dx.doi.org/10.1371/journal.pone.0144825] [PMID: 26709701] 
[115] 
Yin YP, Shi WH, Deng K, et al. Combinations of proteasome inhibitors with obatoclax are effective for small cell lung cancer. Acta Pharmacol Sin  2021; 42(8): 1298-310.
[PMID: 33139838] 
[116] 
Taromi S, Lewens F, Arsenic R, et al. Proteasome inhibitor bortezomib enhances the effect of standard chemotherapy in small cell lung cancer. Oncotarget  2017; 8(57): 97061-78.
[http://dx.doi.org/10.18632/oncotarget.21221] [PMID: 29228593] 
[117] 
Zhao Y, Foster NR, Meyers JP, Thomas SP, Northfelt DW, Rowland KM Jr. A phase I/II study of bortezomib in combination with paclitaxel, carboplatin, and concurrent thoracic radiation therapy for non-small-cell lung cancer: North Central Cancer Treatment Group (NCCTG)-N0321. J Thor Oncolo: Off Pub Int Ass Study of Lung Cancer  2015; 10(1): 172-80.
[118] 
Arnold SM, Chansky K, Leggas M, et al. Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553). Invest New Drugs  2017; 35(5): 608-15.
[http://dx.doi.org/10.1007/s10637-017-0441-4] [PMID: 28204981] 
[119] 
Jones DR, Moskaluk CA, Gillenwater HH, Petroni GR, Burks SG, Philips J. Phase I trial of induction histone deacetylase and proteasome inhibition followed by surgery in non-small-cell lung cancer. J Thor Oncolo: Off Pub Int Ass Study of Lung Cancer  2012; 7(11): 1683-90.
[120] 
Denlinger CE, Keller MD, Mayo MW, Broad RM, Jones DR. Combined proteasome and histone deacetylase inhibition in non-small cell lung cancer. J Thorac Cardiovasc Surg  2004; 127(4): 1078-86.
[http://dx.doi.org/10.1016/S0022-5223(03)01321-7] [PMID: 15052205] 
[121] 
Denlinger CE, Rundall BK, Keller MD, Jones DR. Proteasome inhibition sensitizes non-small-cell lung cancer to gemcitabine-induced apoptosis. The Annals of thoracic surgery  2004; 78(4): 1207-14.
[http://dx.doi.org/10.1016/j.athoracsur.2004.04.029] 
[122] 
Kusumoto S, Sugiyama T, Ando K, et al. Combination effect between bortezomib and tumor necrosis factor alpha on gefitinib-resistant non-small cell lung cancer cell lines. Anticancer Res  2009; 29(6): 2315-22.
[PMID: 19528497] 
[123] 
Hanke NT, Imler E, Marron MT, Seligmann BE, Garland LL, Baker AF. Characterization of carfilzomib-resistant non-small cell lung cancer cell lines. J Cancer Res Clin Oncol  2018; 144(7): 1317-27.
[http://dx.doi.org/10.1007/s00432-018-2662-0] [PMID: 29766327] 
[124] 
de Wilt LH, Jansen G, Assaraf YG, et al. Proteasome-based mechanisms of intrinsic and acquired bortezomib resistance in non-small cell lung cancer. Biochem Pharmacol  2012; 83(2): 207-17.
[http://dx.doi.org/10.1016/j.bcp.2011.10.009] [PMID: 22027222] 
[125] 
Bold RJ, Virudachalam S, McConkey DJ. Chemosensitization of pancreatic cancer by inhibition of the 26S proteasome. J Surg Res  2001; 100(1): 11-7.
[http://dx.doi.org/10.1006/jsre.2001.6194] [PMID: 11516199] 
[126] 
Nawrocki ST, Carew JS, Pino MS, et al. Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. Cancer Res  2005; 65(24): 11658-66.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2370] [PMID: 16357177] 
[127] 
Wente MN, Eibl G, Reber HA, Friess H, Büchler MW, Hines OJ. The proteasome inhibitor MG132 induces apoptosis in human pancreatic cancer cells. Oncol Rep  2005; 14(6): 1635-8.
[http://dx.doi.org/10.3892/or.14.6.1635] [PMID: 16273269] 
[128] 
Li X, Liang M, Jiang J, et al. Combined inhibition of autophagy and Nrf2 signaling augments bortezomib-induced apoptosis by increasing ROS production and ER stress in pancreatic cancer cells. Int J Biol Sci  2018; 14(10): 1291-305.
[http://dx.doi.org/10.7150/ijbs.26776] [PMID: 30123077] 
[129] 
Fahy BN, Schlieman MG, Virudachalam S, Bold RJ. Schedule-dependent molecular effects of the proteasome inhibitor bortezomib and gemcitabine in pancreatic cancer. J Surg Res  2003; 113(1): 88-95.
[http://dx.doi.org/10.1016/S0022-4804(03)00201-4] [PMID: 12943815] 
[130] 
Gong L, Yang B, Xu M, et al. Bortezomib-induced apoptosis in cultured pancreatic cancer cells is associated with ceramide production. Cancer Chemother Pharmacol  2014; 73(1): 69-77.
[http://dx.doi.org/10.1007/s00280-013-2318-3] [PMID: 24190701] 
[131] 
Sloss CM, Wang F, Liu R, et al. Proteasome inhibition activates epidermal growth factor receptor (EGFR) and EGFR-independent mitogenic kinase signaling pathways in pancreatic cancer cells. Clin Cancer Res  2008; 14(16): 5116-23.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-4506] [PMID: 18698029] 
[132] 
Nawrocki ST, Carew JS, Pino MS, et al. Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Res  2006; 66(7): 3773-81.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2961] [PMID: 16585204] 
[133] 
Awasthi N, Schwarz MA, Schwarz RE. Proteasome inhibition enhances antitumour effects of gemcitabine in experimental pancreatic cancer. HPB (Oxford)  2009; 11(7): 600-5.
[http://dx.doi.org/10.1111/j.1477-2574.2009.00109.x] [PMID: 20495713] 
[134] 
Lee JK, Ryu JK, Yang KY, et al. Effects and mechanisms of the combination of suberoylanilide hydroxamic acid and bortezomib on the anticancer property of gemcitabine in pancreatic cancer. Pancreas  2011; 40(6): 966-73.
[http://dx.doi.org/10.1097/MPA.0b013e3182156d5a] [PMID: 21487323] 
[135] 
Bai J, Demirjian A, Sui J, Marasco W, Callery MP. Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341 synergistically induce apoptosis in pancreatic cancer cells. Biochem Biophys Res Commun  2006; 348(4): 1245-53.
[http://dx.doi.org/10.1016/j.bbrc.2006.07.185] [PMID: 16904634] 
[136] 
Belalcazar A, Shaib WL, Farren MR, et al. Inhibiting heat shock protein 90 and the ubiquitin-proteasome pathway impairs metabolic homeostasis and leads to cell death in human pancreatic cancer cells. Cancer  2017; 123(24): 4924-33.
[http://dx.doi.org/10.1002/cncr.30944] [PMID: 28841232] 
[137] 
Chiu HW, Lin SW, Lin LC, et al. Synergistic antitumor effects of radiation and proteasome inhibitor treatment in pancreatic cancer through the induction of autophagy and the downregulation of TRAF6. Cancer Lett  2015; 365(2): 229-39.
[http://dx.doi.org/10.1016/j.canlet.2015.05.025] [PMID: 26052093] 
[138] 
Min H, Xu M, Chen ZR, et al. Bortezomib induces protective autophagy through AMP-activated protein kinase activation in cultured pancreatic and colorectal cancer cells. Cancer Chemother Pharmacol  2014; 74(1): 167-76.
[http://dx.doi.org/10.1007/s00280-014-2451-7] [PMID: 24842158] 
[139] 
Awada A, Albanell J, Canney PA, et al. Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study. Br J Cancer  2008; 98(9): 1500-7.
[http://dx.doi.org/10.1038/sj.bjc.6604347] [PMID: 18454159] 
[140] 
Soppimath K, Pejaver S, Patel KR, Dasaradhi L, Sodum R, Desu H. InventorsStable botezomib formulation. US 20120322763, 2012.
[141] 
Valik M, Gabriel R, Vraspir P, Lukas D. InventorsProcess for the preparation of ixazomib citrate.  US 20200190119, 2020.
[142] 
Pasqua L, Leggio A, Liguori A, Morelli C. InventorsBortezomib-based delivery system US 20180127441, 2018.
[143] 
Luehr G, Anik ST, Peng G, Dotsenko I, Phiasivongsa P, Romanini D. Inventors Pegylated carfilzomib compounds. US 20170340746, 2017.
[144] 
Frasco MF, Almeida GM, Santos-Silva F, Pereira MdoC, Coelho MA. Transferrin surface-modified PLGA nanoparticles-mediated delivery of a proteasome inhibitor to human pancreatic cancer cells. J Biomed Mater Res A  2015; 103(4): 1476-84.
[http://dx.doi.org/10.1002/jbm.a.35286] [PMID: 25046528] 
[145] 
Park JE, Park J, Jun Y, et al. Expanding therapeutic utility of carfilzomib for breast cancer therapy by novel albumin-coated nanocrystal formulation. J Control Rel: Off J Controlled Release Society  2019; 302: 148-59.
[http://dx.doi.org/10.1016/j.jconrel.2019.04.006] 
[146] 
Coelho SC, Almeida GM, Santos-Silva F, Pereira MC, Coelho MA. Enhancing the efficiency of bortezomib conjugated to pegylated gold nanoparticles: an in vitro study on human pancreatic cancer cells and adenocarcinoma human lung alveolar basal epithelial cells. Expert Opin Drug Deliv  2016; 13(8): 1075-81.
[http://dx.doi.org/10.1080/17425247.2016.1178234] [PMID: 27087021] 
[147] 
Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res  2007; 67(13): 6383-91.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4086] [PMID: 17616698] 
[148] 
Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP. Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res  2008; 68(18): 7283-92.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6246] [PMID: 18794115] 
[149] 
Liu L, Fu Y, Zheng Y, Ma M, Wang C. Curcumin inhibits proteasome activity in triple-negative breast cancer cells through regulating p300/miR-142-3p/PSMB5 axis. Phytomedicine: IntJ Phytother Phytopharmacol  2020; 78-153312.
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DOI https://dx.doi.org/10.2174/1574892816666211202154536	Print ISSN 1574-8928
Publisher Name Bentham Science Publisher	Online ISSN 2212-3970
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