Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

The Curcumin Analog EF24 is Highly Active Against Chemotherapy- Resistant Melanoma Cells

Author(s): Yonghan He*, Wen Li, Junling Zhang, Yang Yang, Yawei Qian and Daohong Zhou

Volume 21, Issue 7, 2021

Published on: 03 March, 2021

Page: [608 - 618] Pages: 11

DOI: 10.2174/1568009621666210303092921

Price: $65

Abstract

Background: Malignant melanoma (MM) is an aggressive type of skin cancer with a poor prognosis, because MM cells are characterized by unresponsiveness to chemotherapy.

Objective: In this study, we evaluated the effectiveness of several curcumin analogs on four MM cell lines (SK-MEL-28, MeWo, A-375, and CHL-1) and explored their underlying mechanisms of action.

Methods: Cell viability was measured by a Tetrazolium-based MTS assay. Cell apoptosis, reactive oxygen species (ROS), and cell cycle were assayed by flow cytometry. Protein levels were assayed by western blotting.

Results: MM cells are quite resistant to the conventional chemotherapeutics cisplatin and dacarbazine, and the targeted therapy drug vemurafinib. Among the curcumin analogs, EF24 is the most potent compound against the resistant MM cells. EF24 dose and time-dependently reduced the viability of MM cells by inducing apoptosis. Although EF24 did not increase the production of reactive oxygen species (ROS), it upregulated the endoplasmic reticulum (ER) stress marker BiP, but downregulated the unfolded protein response (UPR) signaling. Moreover, treatment of MM cells with EF24 downregulated the expression of the anti-apoptotic protein Bcl-2, as well as the inhibitor of apoptosis proteins (IAPs) XIAP, cIAP1, and Birc7, which are known to protect MM cells from apoptosis. The downregulation of Bcl-2 and IAP expression by EF24 was associated with the inhibition of the NF-κB pathway.

Conclusion: These findings demonstrate that EF24 is a potent anti-MM agent. The anti-MM effect is likely mediated by the suppression of UPR and the NF-κB pathway.

Keywords: Bcl-2, EF24, IAPs, malignant melanoma, NF-κB, unfolded protein response.

Graphical Abstract

[1]
MacKie, R.M.; Hauschild, A.; Eggermont, A.M.M. Epidemiology of invasive cutaneous melanoma. Ann. Oncol., 2009, 20(Suppl. 6), vi1-vi7.
[http://dx.doi.org/10.1093/annonc/mdp252] [PMID: 19617292]
[2]
Duncan, L.M. The classification of cutaneous melanoma. Hematol. Oncol. Clin. North Am., 2009, 23(3), 501-513, ix.
[http://dx.doi.org/10.1016/j.hoc.2009.03.013] [PMID: 19464599]
[3]
Markovic, S.N.; Erickson, L.A.; Rao, R.D.; Weenig, R.H.; Pockaj, B.A.; Bardia, A.; Vachon, C.M.; Schild, S.E.; McWilliams, R.R.; Hand, J.L.; Laman, S.D.; Kottschade, L.A.; Maples, W.J.; Pittelkow, M.R.; Pulido, J.S.; Cameron, J.D.; Creagan, E.T. Malignant melanoma in the 21st century, part 1: Epidemiology, risk factors, screening, prevention, and diagnosis. Mayo Clin. Proc., 2007, 82(3), 364-380.
[http://dx.doi.org/10.1016/S0025-6196(11)61033-1] [PMID: 17352373]
[4]
Sun, W.; Schuchter, L.M. Metastatic melanoma. Curr. Treat. Options Oncol., 2001, 2(3), 193-202.
[http://dx.doi.org/10.1007/s11864-001-0033-5] [PMID: 12057119]
[5]
Elder, D.E. Melanoma progression. Pathology, 2016, 48(2), 147-154.
[http://dx.doi.org/10.1016/j.pathol.2015.12.002] [PMID: 27020387]
[6]
Atkins, M.B.; Hsu, J.; Lee, S.; Cohen, G.I.; Flaherty, L.E.; Sosman, J.A.; Sondak, V.K.; Kirkwood, J.M. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): A trial coordinated by the Eastern Cooperative Oncology Group. J. Clin. Oncol., 2008, 26(35), 5748-5754.
[http://dx.doi.org/10.1200/JCO.2008.17.5448] [PMID: 19001327]
[7]
Kim, A.; Cohen, M.S. The discovery of vemurafenib for the treatment of BRAF-mutated metastatic melanoma. Expert Opin. Drug Discov., 2016, 11(9), 907-916.
[http://dx.doi.org/10.1080/17460441.2016.1201057] [PMID: 27327499]
[8]
Long, G.V.; Hauschild, A.; Santinami, M.; Atkinson, V.; Mandalà, M.; Chiarion-Sileni, V.; Larkin, J.; Nyakas, M.; Dutriaux, C.; Haydon, A.; Robert, C.; Mortier, L.; Schachter, J.; Schadendorf, D.; Lesimple, T.; Plummer, R.; Ji, R.; Zhang, P.; Mookerjee, B.; Legos, J.; Kefford, R.; Dummer, R.; Kirkwood, J.M. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N. Engl. J. Med., 2017, 377(19), 1813-1823.
[http://dx.doi.org/10.1056/NEJMoa1708539] [PMID: 28891408]
[9]
Nevala, W.K.; Buhrow, S.A.; Knauer, D.J.; Reid, J.M.; Atanasova, E.A.; Markovic, S.N. Antibody-targeted chemotherapy for the treatment of melanoma. Cancer Res., 2016, 76(13), 3954-3964.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-3131] [PMID: 27197186]
[10]
Weiss, S.A.; Wolchok, J.D.; Sznol, M. Immunotherapy of melanoma: Facts and hopes. Clin. Cancer Res., 2019, 25(17), 5191-5201.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-1550] [PMID: 30923036]
[11]
Lim, S.Y.; Menzies, A.M.; Rizos, H. Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma. Cancer, 2017, 123(S11), 2118-2129.
[http://dx.doi.org/10.1002/cncr.30435] [PMID: 28543695]
[12]
Roesch, A.; Vultur, A.; Bogeski, I.; Wang, H.; Zimmermann, K.M.; Speicher, D.; Körbel, C.; Laschke, M.W.; Gimotty, P.A.; Philipp, S.E.; Krause, E.; Pätzold, S.; Villanueva, J.; Krepler, C.; Fukunaga-Kalabis, M.; Hoth, M.; Bastian, B.C.; Vogt, T.; Herlyn, M. Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells. Cancer Cell, 2013, 23(6), 811-825.
[http://dx.doi.org/10.1016/j.ccr.2013.05.003] [PMID: 23764003]
[13]
Smalley, K.S.M.; Haass, N.K.; Brafford, P.A.; Lioni, M.; Flaherty, K.T.; Herlyn, M. Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Mol. Cancer Ther., 2006, 5(5), 1136-1144.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0084] [PMID: 16731745]
[14]
Soengas, M.S.; Lowe, S.W. Apoptosis and melanoma chemoresistance. Oncogene, 2003, 22(20), 3138-3151.
[http://dx.doi.org/10.1038/sj.onc.1206454] [PMID: 12789290]
[15]
Najem, A.; Krayem, M.; Salès, F.; Hussein, N.; Badran, B.; Robert, C.; Awada, A.; Journe, F.; Ghanem, G.E. P53 and MITF/Bcl-2 identified as key pathways in the acquired resistance of NRAS-mutant melanoma to MEK inhibition. Eur. J. Cancer, 2017, 83, 154-165.
[http://dx.doi.org/10.1016/j.ejca.2017.06.033] [PMID: 28738256]
[16]
Eberle, J.; Kurbanov, B.M.; Hossini, A.M.; Trefzer, U.; Fecker, L.F. Overcoming apoptosis deficiency of melanoma-hope for new therapeutic approaches. Drug Resist. Updat., 2007, 10(6), 218-234.
[http://dx.doi.org/10.1016/j.drup.2007.09.001] [PMID: 18054518]
[17]
Chang, H.; Schimmer, A.D. Livin/melanoma inhibitor of apoptosis protein as a potential therapeutic target for the treatment of malignancy. Mol. Cancer Ther., 2007, 6(1), 24-30.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0443] [PMID: 17237263]
[18]
Schmollinger, J.C.; Dranoff, G. Targeting melanoma inhibitor of apoptosis protein with cancer immunotherapy. Apoptosis, 2004, 9(3), 309-313.
[http://dx.doi.org/10.1023/B:APPT.0000025807.59668.5e] [PMID: 15258462]
[19]
Mirzaei, H.; Naseri, G.; Rezaee, R.; Mohammadi, M.; Banikazemi, Z.; Mirzaei, H.R.; Salehi, H.; Peyvandi, M.; Pawelek, J.M.; Sahebkar, A. Curcumin: A new candidate for melanoma therapy? Int. J. Cancer, 2016, 139(8), 1683-1695.
[http://dx.doi.org/10.1002/ijc.30224] [PMID: 27280688]
[20]
Song, X.; Gao, T.; Lei, Q.; Zhang, L.; Yao, Y.; Xiong, J. Piperlongumine induces apoptosis in human melanoma cells via reactive oxygen species mediated mitochondria disruption. Nutr. Cancer, 2018, 70(3), 502-511.
[http://dx.doi.org/10.1080/01635581.2018.1445769] [PMID: 29543494]
[21]
Caunii, A.; Oprean, C.; Cristea, M.; Ivan, A.; Danciu, C.; Tatu, C.; Paunescu, V.; Marti, D.; Tzanakakis, G.; Spandidos, D.A.; Tsatsakis, A.; Susan, R.; Soica, C.; Avram, S.; Dehelean, C. Effects of ursolic and oleanolic on SK-MEL-2 melanoma cells: In vitro and in vivo assays. Int. J. Oncol., 2017, 51(6), 1651-1660.
[http://dx.doi.org/10.3892/ijo.2017.4160] [PMID: 29039461]
[22]
Bindseil, K.U.; Jakupovic, J.; Wolf, D.; Lavayre, J.; Leboul, J.; van der Pyl, D. Pure compound libraries; a new perspective for natural product based drug discovery. Drug Discov. Today, 2001, 6(16), 840-847.
[http://dx.doi.org/10.1016/S1359-6446(01)01856-6] [PMID: 11495757]
[23]
Vuorelaa, P.; Leinonenb, M.; Saikkuc, P.; Tammelaa, P.; Rauhad, J-P.; Wennberge, T.; Vuorela, H. Natural products in the process of finding new drug candidates. Curr. Med. Chem., 2004, 11(11), 1375-1389.
[http://dx.doi.org/10.2174/0929867043365116] [PMID: 15180572]
[24]
Lam, K.S. New aspects of natural products in drug discovery. Trends Microbiol., 2007, 15(6), 279-289.
[http://dx.doi.org/10.1016/j.tim.2007.04.001] [PMID: 17433686]
[25]
Ouyang, L.; Luo, Y.; Tian, M.; Zhang, S-Y.; Lu, R.; Wang, J-H.; Kasimu, R.; Li, X. Plant natural products: from traditional compounds to new emerging drugs in cancer therapy. Cell Prolif., 2014, 47(6), 506-515.
[http://dx.doi.org/10.1111/cpr.12143] [PMID: 25377084]
[26]
Shanmugam, M.K.; Rane, G.; Kanchi, M.M.; Arfuso, F.; Chinnathambi, A.; Zayed, M.E.; Alharbi, S.A.; Tan, B.K.H.; Kumar, A.P.; Sethi, G. The multifaceted role of curcumin in cancer prevention and treatment. Molecules, 2015, 20(2), 2728-2769.
[http://dx.doi.org/10.3390/molecules20022728] [PMID: 25665066]
[27]
Ak, T.; Gülçin, I. Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact., 2008, 174(1), 27-37.
[http://dx.doi.org/10.1016/j.cbi.2008.05.003] [PMID: 18547552]
[28]
Jurenka, J.S. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern. Med. Rev., 2009, 14(2), 141-153.
[PMID: 19594223]
[29]
Moghadamtousi, S.Z.; Kadir, H.A.; Hassandarvish, P.; Tajik, H.; Abubakar, S.; Zandi, K. A review on antibacterial, antiviral, and antifungal activity of curcumin. BioMed Res. Int., 2014, 2014, 186864.
[http://dx.doi.org/10.1155/2014/186864] [PMID: 24877064]
[30]
Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: problems and promises. Mol. Pharm., 2007, 4(6), 807-818.
[http://dx.doi.org/10.1021/mp700113r] [PMID: 17999464]
[31]
Adams, B.K.; Cai, J.; Armstrong, J.; Herold, M.; Lu, Y.J.; Sun, A.; Snyder, J.P.; Liotta, D.C.; Jones, D.P.; Shoji, M. EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anticancer Drugs, 2005, 16(3), 263-275.
[http://dx.doi.org/10.1097/00001813-200503000-00005] [PMID: 15711178]
[32]
Madan, E.; Parker, T.M.; Bauer, M.R.; Dhiman, A.; Pelham, C.J.; Nagane, M.; Kuppusamy, M.L.; Holmes, M.; Holmes, T.R.; Shaik, K.; Shee, K.; Kiparoidze, S.; Smith, S.D.; Park, Y.A.; Gomm, J.J.; Jones, L.J.; Tomás, A.R.; Cunha, A.C.; Selvendiran, K.; Hansen, L.A.; Fersht, A.R.; Hideg, K.; Gogna, R.; Kuppusamy, P. The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53. J. Biol. Chem., 2018, 293(12), 4262-4276.
[http://dx.doi.org/10.1074/jbc.RA117.000950] [PMID: 29382728]
[33]
Dinkova-Kostova, A.T.; Cory, A.H.; Bozak, R.E.; Hicks, R.J.; Cory, J.G. Bis(2-hydroxybenzylidene)acetone, a potent inducer of the phase 2 response, causes apoptosis in mouse leukemia cells through a p53-independent, caspase-mediated pathway. Cancer Lett., 2007, 245(1-2), 341-349.
[http://dx.doi.org/10.1016/j.canlet.2006.01.024] [PMID: 16517063]
[34]
Tamvakopoulos, C.; Dimas, K.; Sofianos, Z.D.; Hatziantoniou, S.; Han, Z.; Liu, Z-L.; Wyche, J.H.; Pantazis, P. Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin. Clin. Cancer Res., 2007, 13(4), 1269-1277.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1839] [PMID: 17317839]
[35]
He, Y.; Li, W.; Hu, G.; Sun, H.; Kong, Q. Bioactivities of EF24, a novel curcumin analog: A review. Front. Oncol., 2018, 8, 614.
[http://dx.doi.org/10.3389/fonc.2018.00614] [PMID: 30619754]
[36]
Adams, B.K.; Ferstl, E.M.; Davis, M.C.; Herold, M.; Kurtkaya, S.; Camalier, R.F.; Hollingshead, M.G.; Kaur, G.; Sausville, E.A.; Rickles, F.R.; Snyder, J.P.; Liotta, D.C.; Shoji, M. Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents. Bioorg. Med. Chem., 2004, 12(14), 3871-3883.
[http://dx.doi.org/10.1016/j.bmc.2004.05.006] [PMID: 15210154]
[37]
Li, W.; He, Y.; Zhang, R.; Zheng, G.; Zhou, D. The curcumin analog EF24 is a novel senolytic agent. Aging (Albany NY), 2019, 11(2), 771-782.
[http://dx.doi.org/10.18632/aging.101787] [PMID: 30694217]
[38]
Chen, W.; Zou, P.; Zhao, Z.; Chen, X.; Fan, X.; Vinothkumar, R.; Cui, R.; Wu, F.; Zhang, Q.; Liang, G.; Ji, J. Synergistic antitumor activity of rapamycin and EF24 via increasing ROS for the treatment of gastric cancer. Redox Biol., 2016, 10, 78-89.
[http://dx.doi.org/10.1016/j.redox.2016.09.006] [PMID: 27697670]
[39]
Chen, X.; Dai, X.; Zou, P.; Chen, W.; Rajamanickam, V.; Feng, C.; Zhuge, W.; Qiu, C.; Ye, Q.; Zhang, X.; Liang, G. Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer. Br. J. Pharmacol., 2017, 174(10), 1131-1146.
[http://dx.doi.org/10.1111/bph.13765] [PMID: 28255993]
[40]
Lee, A.S. The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods, 2005, 35(4), 373-381.
[http://dx.doi.org/10.1016/j.ymeth.2004.10.010] [PMID: 15804610]
[41]
Hetz, C.; Papa, F.R. The unfolded protein response and cell fate control. Mol. Cell, 2018, 69(2), 169-181.
[http://dx.doi.org/10.1016/j.molcel.2017.06.017] [PMID: 29107536]
[42]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[43]
Singh, R.; Letai, A.; Sarosiek, K. Regulation of apoptosis in health and disease: The balancing act of BCL-2 family proteins. Nat. Rev. Mol. Cell Biol., 2019, 20(3), 175-193.
[http://dx.doi.org/10.1038/s41580-018-0089-8] [PMID: 30655609]
[44]
Igney, F.H.; Krammer, P.H. Death and anti-death: tumour resistance to apoptosis. Nat. Rev. Cancer, 2002, 2(4), 277-288.
[http://dx.doi.org/10.1038/nrc776] [PMID: 12001989]
[45]
Lee, E.F.; Harris, T.J.; Tran, S.; Evangelista, M.; Arulananda, S.; John, T.; Ramnac, C.; Hobbs, C.; Zhu, H.; Gunasingh, G.; Segal, D.; Behren, A.; Cebon, J.; Dobrovic, A.; Mariadason, J.M.; Strasser, A.; Rohrbeck, L.; Haass, N.K.; Herold, M.J.; Fairlie, W.D. BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival. Cell Death Dis., 2019, 10(5), 342.
[http://dx.doi.org/10.1038/s41419-019-1568-3] [PMID: 31019203]
[46]
Deveraux, Q.L.; Reed, J.C. IAP family proteins- suppressors of apoptosis. Genes Dev., 1999, 13(3), 239-252.
[http://dx.doi.org/10.1101/gad.13.3.239] [PMID: 9990849]
[47]
Engesæter, B.O.; Sathermugathevan, M.; Hellenes, T.; Engebråten, O.; Holm, R.; Flørenes, V.A.; Mælandsmo, G.M. Targeting inhibitor of apoptosis proteins in combination with dacarbazine or TRAIL in melanoma cells. Cancer Biol. Ther., 2011, 12(1), 47-58.
[http://dx.doi.org/10.4161/cbt.12.1.15714] [PMID: 21508672]
[48]
Vucic, D.; Stennicke, H.R.; Pisabarro, M.T.; Salvesen, G.S.; Dixit, V.M. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr. Biol., 2000, 10(21), 1359-1366.
[http://dx.doi.org/10.1016/S0960-9822(00)00781-8] [PMID: 11084335]
[49]
Wang, H.; Tan, S.S.; Wang, X.Y.; Liu, D.H.; Yu, C.S.; Bai, Z.L.; He, D.L.; Zhao, J. Silencing livin gene by siRNA leads to apoptosis induction, cell cycle arrest, and proliferation inhibition in malignant melanoma LiBr cells. Acta Pharmacol. Sin., 2007, 28(12), 1968-1974.
[http://dx.doi.org/10.1111/j.1745-7254.2007.00724.x] [PMID: 18031611]
[50]
Catz, S.D.; Johnson, J.L. Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene, 2001, 20(50), 7342-7351.
[http://dx.doi.org/10.1038/sj.onc.1204926] [PMID: 11704864]
[51]
Oeckinghaus, A.; Ghosh, S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol., 2009, 1(4), a000034.
[http://dx.doi.org/10.1101/cshperspect.a000034] [PMID: 20066092]
[52]
Tentori, L.; Lacal, P.M.; Graziani, G. Challenging resistance mechanisms to therapies for metastatic melanoma. Trends Pharmacol. Sci., 2013, 34(12), 656-666.
[http://dx.doi.org/10.1016/j.tips.2013.10.003] [PMID: 24210882]
[53]
Chinembiri, T.N.; du Plessis, L.H.; Gerber, M.; Hamman, J.H.; du Plessis, J. Review of natural compounds for potential skin cancer treatment. Molecules, 2014, 19(8), 11679-11721.
[http://dx.doi.org/10.3390/molecules190811679] [PMID: 25102117]
[54]
Anand, P.; Thomas, S.G.; Kunnumakkara, A.B.; Sundaram, C.; Harikumar, K.B.; Sung, B.; Tharakan, S.T.; Misra, K.; Priyadarsini, I.K.; Rajasekharan, K.N.; Aggarwal, B.B. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem. Pharmacol., 2008, 76(11), 1590-1611.
[http://dx.doi.org/10.1016/j.bcp.2008.08.008] [PMID: 18775680]
[55]
Maheshwari, R.K.; Singh, A.K.; Gaddipati, J.; Srimal, R.C. Multiple biological activities of curcumin: A short review. Life Sci., 2006, 78(18), 2081-2087.
[http://dx.doi.org/10.1016/j.lfs.2005.12.007] [PMID: 16413584]
[56]
Kasinski, A.L.; Du, Y.; Thomas, S.L.; Zhao, J.; Sun, S-Y.; Khuri, F.R.; Wang, C-Y.; Shoji, M.; Sun, A.; Snyder, J.P.; Liotta, D.; Fu, H. Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin. Mol. Pharmacol., 2008, 74(3), 654-661.
[http://dx.doi.org/10.1124/mol.108.046201] [PMID: 18577686]
[57]
Sun, S-C. The non-canonical NF-κB pathway in immunity and inflammation. Nat. Rev. Immunol., 2017, 17(9), 545-558.
[http://dx.doi.org/10.1038/nri.2017.52] [PMID: 28580957]
[58]
Viatour, P.; Bentires-Alj, M.; Chariot, A.; Deregowski, V.; de Leval, L.; Merville, M-P.; Bours, V. NF- kappa B2/p100 induces Bcl-2 expression. Leukemia, 2003, 17(7), 1349-1356.
[http://dx.doi.org/10.1038/sj.leu.2402982] [PMID: 12835724]
[59]
Zou, T.; Rao, J.N.; Guo, X.; Liu, L.; Zhang, H.M.; Strauch, E.D.; Bass, B.L.; Wang, J-Y. NF-kappaB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion. Am. J. Physiol. Cell Physiol., 2004, 286(5), C1009-C1018.
[http://dx.doi.org/10.1152/ajpcell.00480.2003] [PMID: 15075199]
[60]
Yang, C.H.; Yue, J.; Sims, M.; Pfeffer, L.M. The curcumin analog EF24 targets NF-κB and miRNA-21, and has potent anticancer activity in vitro and in vivo. PLoS One, 2013, 8(8), e71130.
[http://dx.doi.org/10.1371/journal.pone.0071130] [PMID: 23940701]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy