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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Autophagic Vacuole Secretion Triggered by Chidamide Participates in TRAIL Apoptosis Effect in Breast Cancer Cells

Author(s): Weiqiang Zhou*, Han Han, Junnan Xu, Tao Sun* and Xiuyan Feng*

Volume 27, Issue 20, 2021

Published on: 11 August, 2020

Page: [2366 - 2380] Pages: 15

DOI: 10.2174/1381612826666200811175513

Price: $65

Abstract

Background: Breast cancer is one of the most prevalent diseases threatening women's health today. Indepth research on breast cancer (BC) pathogenesis and prevention and treatment methods are gradually receiving attention. Chidamide is a novel histone deacetylase inhibitor (HDACi) that depresses the function of histone deacetylase, consequently affecting the growth of BC cells through epigenetic modification. However, preclinical and clinical studies show that chidamide is ineffective in long-term treatment. We demonstrated in previous experiments that TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in BC cells and is significantly less non-toxic to normal cells than chidamide. Therefore, in this study, we treated BC cells with chidamide and TRAIL to explore a novel option to reduce the clinical toxicity through augmenting the sensitivity for BC cells.

Methods and Results: Results from the MTT and cell viability assays indicated that the combination of chidamide and TRAIL in MCF-7 and MDA-MB-231 cells induced BC cell death, while maintaining a reduced concentration of chidamide. Autophagy assay and annexin V analysis showed that the autophagosome microtubuleassociated protein1light chain3-II (LC3-II) was abnormally increased and much more early and late phase of apoptotic cells appeared during chidamide and TRAIL induction. Anti-tumor assays in a BC tumor xenograft model displayed that the mixture of chidamide and TRAIL exhibited stronger effects on inhibiting tumor growth. The data from real-time PCR and western blotting showed that the cytotoxic effect correlated with the expressions of related apoptosis and autophagy factors.

Conclusion: Our data are the first to demonstrate the synergistic effects of chidamide and TRAIL in BC cells, specifically, the pharmacological effects on cell death induction. These results lay a solid experimental and theoretical basis to solve the clinical resistance of chidamide.

Keywords: Chidamide, TRAIL, apoptosis, drug resistance, breast cancer, HDACi.

« Previous Next »
[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Greer YE, Gilbert SF, Gril B, et al. MEDI3039, a novel highly potent tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2 agonist, causes regression of orthotopic tumors and inhibits outgrowth of metastatic triple-negative breast cancer. Breast Cancer Res 2019; 21(1): 27.
[http://dx.doi.org/10.1186/s13058-019-1116-1] [PMID: 30777098]
[3]
Gao A, Sun T, Ma G, et al. LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway. Nat Commun 2018; 9(1): 4180.
[http://dx.doi.org/10.1038/s41467-018-06309-8] [PMID: 30301939]
[4]
Coté D, Eustace A, Toomey S, et al. Germline single nucleotide polymorphisms in ERBB3 and BARD1 genes result in a worse relapse free survival response for HER2-positive breast cancer patients treated with adjuvant based docetaxel, carboplatin and trastuzumab (TCH). PLoS One 2018; 13(8)e0200996
[http://dx.doi.org/10.1371/journal.pone.0200996] [PMID: 30071039]
[5]
Elias D, Vever H, Lænkholm AV, et al. Correction: Gene expression profiling identifies FYN as an important molecule in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy. Oncogene 2018; 37(41): 5585-6.
[http://dx.doi.org/10.1038/s41388-018-0495-6] [PMID: 30242243]
[6]
Palomeras S, Ruiz-Martínez S, Puig T. Targeting breast cancer stem cells to overcome treatment resistance. Molecules 2018; 23(9)e2193
[http://dx.doi.org/10.3390/molecules23092193] [PMID: 30200262]
[7]
Kim HS, Kacew S, Lee BM. Genetic and epigenetic cancer chemoprevention on molecular targets during multistage carcinogenesis. Arch Toxicol 2016; 90(10): 2389-404.
[http://dx.doi.org/10.1007/s00204-016-1813-9] [PMID: 27538406]
[8]
Kazanets A, Shorstova T, Hilmi K, Marques M, Witcher M. Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential. Biochim Biophys Acta 2016; 1865(2): 275-88.
[PMID: 27085853]
[9]
Feinberg AP, Koldobskiy MA, Göndör A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet 2016; 17(5): 284-99.
[http://dx.doi.org/10.1038/nrg.2016.13] [PMID: 26972587]
[10]
Rifaï K, Idrissou M, Penault-Llorca F, Bignon YJ, Bernard-Gallon D. Breaking down the Contradictory Roles of Histone Deacetylase SIRT1 in Human Breast Cancer. Cancers (Basel) 2018; 10(11)e409
[http://dx.doi.org/10.3390/cancers10110409] [PMID: 30380732]
[11]
Han YJ, Boatman SM, Zhang J, et al. LncRNA BLAT1 is upregulated in basal-like breast cancer through epigenetic modifications. Sci Rep 2018; 8(1): 15572.
[http://dx.doi.org/10.1038/s41598-018-33629-y] [PMID: 30349062]
[12]
Mao J, Li S, Zhao H, et al. Effects of chidamide and its combination with decitabine on proliferation and apoptosis of leukemia cell lines. Am J Transl Res 2018; 10(8): 2567-78.
[PMID: 30210693]
[13]
Bai X, Jiang H, Han G, He Q. Chidamide suppresses the glycolysis of triple negative breast cancer cells partially by targeting the miR-33a-5p-LDHA axis. Mol Med Rep 2019; 20(2): 1857-65.
[http://dx.doi.org/10.3892/mmr.2019.10425] [PMID: 31257519]
[14]
Liu Z, Chen J, Wang H, et al. Chidamide shows synergistic cytotoxicity with cytarabine via inducing G0/G1 arrest and apoptosis in myelodysplastic syndromes. Am J Transl Res 2017; 9(12): 5631-42.
[PMID: 29312515]
[15]
Zhang H, Li L, Li M, et al. Combination of betulinic acid and chidamide inhibits acute myeloid leukemia by suppression of the HIF1α pathway and generation of reactive oxygen species. Oncotarget 2017; 8(55): 94743-58.
[http://dx.doi.org/10.18632/oncotarget.21889] [PMID: 29212263]
[16]
Li Y, Wang Y, Zhou Y, et al. Cooperative effect of chidamide and chemotherapeutic drugs induce apoptosis by DNA damage accumulation and repair defects in acute myeloid leukemia stem and progenitor cells. Clin Epigenetics 2017; 9: 83.
[http://dx.doi.org/10.1186/s13148-017-0377-8] [PMID: 28814980]
[17]
Shankar S, Davis R, Singh KP, Kurzrock R, Ross DD, Srivastava RK. Suberoylanilide hydroxamic acid (Zolinza/vorinostat) sensitizes TRAIL-resistant breast cancer cells orthotopically implanted in BALB/c nude mice. Mol Cancer Ther 2009; 8(6): 1596-605.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-1004] [PMID: 19509267]
[18]
Zhou W, Feng X, Han Han, Guo S, Wang G. Synergistic effects of combined treatment with histone deacetylase inhibitor suberoylanilide hydroxamic acid and TRAIL on human breast cancer cells. Sci Rep 2016; 6: 28004.
[http://dx.doi.org/10.1038/srep28004] [PMID: 27292433]
[19]
Chen Y, Wei L, Zhang X, et al. 3-Bromopyruvate sensitizes human breast cancer cells to TRAIL-induced apoptosis via the phosphorylated AMPK-mediated upregulation of DR5. Oncol Rep 2018; 40(5): 2435-44.
[http://dx.doi.org/10.3892/or.2018.6644] [PMID: 30132536]
[20]
Cano-González A, López-Rivas A. Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells. Biochim Biophys Acta 2016; 1863(8): 2104-14.
[http://dx.doi.org/10.1016/j.bbamcr.2016.05.011] [PMID: 27208428]
[21]
Han H, Zhou H, Li J, Feng X, Zou D, Zhou W. TRAIL DR5-CTSB crosstalk participates in breast cancer autophagy initiated by SAHA. Cell Death Discov 2017; 3: 17052.
[http://dx.doi.org/10.1038/cddiscovery.2017.52] [PMID: 29018571]
[22]
Ekinci E, Rohondia S, Khan R, Dou QP. Repurposing disulfiram as an anti-cancer agent: updated review on literature and patents. Recent Patents Anticancer Drug Discov 2019; 14(2): 113-32.
[http://dx.doi.org/10.2174/1574892814666190514104035] [PMID: 31084595]
[23]
Namee NM, O’Driscoll L. Extracellular vesicles and anti-cancer drug resistance. Biochim Biophys Acta Rev Cancer 2018; 1870(2): 123-36.
[http://dx.doi.org/10.1016/j.bbcan.2018.07.003] [PMID: 30003999]
[24]
Nagini S. Breast cancer: current molecular therapeutic targets and new players. Anticancer Agents Med Chem 2017; 17(2): 152-63.
[http://dx.doi.org/10.2174/1871520616666160502122724] [PMID: 27137076]
[25]
Muraoka M, Akagi T, Ueda A, et al. C/EBPε ΔRS derived from a neutrophil-specific granule deficiency patient interacts with HDAC1 and its dysfunction is restored by trichostatin A. Biochem Biophys Res Commun 2019; 516(1): 293-9.
[http://dx.doi.org/10.1016/j.bbrc.2019.06.130] [PMID: 31256937]
[26]
Zhang Q, Wang T, Geng C, et al. Exploratory clinical study of chidamide, an oral subtype-selective histone deacetylase inhibitor, in combination with exemestane in hormone receptor-positive advanced breast cancer. Chin J Cancer Res 2018; 30(6): 605-12.
[http://dx.doi.org/10.21147/j.issn.1000-9604.2018.06.05] [PMID: 30700929]
[27]
Derakhshani A, Rezaei Z, Safarpour H, et al. Overcoming trastuzumab resistance in HER2-positive breast cancer using combination therapy. J Cell Physiol 2020; 235(4): 3142-56.
[http://dx.doi.org/10.1002/jcp.29216] [PMID: 31566722]
[28]
Yildiz Y, Yaylim-Eraltan I, Arikan S, Ergen HA, Küçücük S, Isbir T. Is there any correlation between TNF-related apoptosis-inducing ligand (TRAIL) genetic variants and breast cancer? Arch Med Sci 2010; 6(6): 932-6.
[http://dx.doi.org/10.5114/aoms.2010.19304] [PMID: 22427769]
[29]
Trivedi R, Mishra DP. Trailing TRAIL Resistance: Novel targets for TRAIL sensitization in cancer cells. Front Oncol 2015; 5: 69.
[http://dx.doi.org/10.3389/fonc.2015.00069] [PMID: 25883904]
[30]
Mowers EE, Sharifi MN, Macleod KF. Autophagy in cancer metastasis. Oncogene 2017; 36(12): 1619-30.
[http://dx.doi.org/10.1038/onc.2016.333] [PMID: 27593926]
[31]
Munson MJ, Ganley IG. MTOR, PIK3C3, and autophagy: Signaling the beginning from the end. Autophagy 2015; 11(12): 2375-6.
[http://dx.doi.org/10.1080/15548627.2015.1106668] [PMID: 26565689]
[32]
Herrero-Martín G, Høyer-Hansen M, García-García C, et al. TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. EMBO J 2009; 28(6): 677-85.
[http://dx.doi.org/10.1038/emboj.2009.8] [PMID: 19197243]
[33]
Tabatabayi ZS, Homayouni-Tabrizi M, Neamati A, Beyramabadi SA. Mn(II) complex of a vitamin B6 Schiff base as an exclusive apoptosis inducer in human MCF7 and HepG2 cancer cells: Synthesis, characterization, and biological studies. J Cell Biochem 2020; 121(3): 2677-89.
[http://dx.doi.org/10.1002/jcb.29488] [PMID: 31680295]
[34]
Jamali T, Kavoosi G, Ardestani SK. In vitro and in vivo anti-breast cancer activity of OEO (Oliveria decumbens vent essential oil) through promoting the apoptosis and immunomodulatory effects. J Ethnopharmacol 2020; 248112313
[http://dx.doi.org/10.1016/j.jep.2019.112313] [PMID: 31655147]
[35]
Rai S, Arasteh M, Jefferson M, et al. The ATG5-binding and coiled coil domains of ATG16L1 maintain autophagy and tissue homeostasis in mice independently of the WD domain required for LC3-associated phagocytosis. Autophagy 2019; 15(4): 599-612.
[http://dx.doi.org/10.1080/15548627.2018.1534507] [PMID: 30403914]
[36]
Cui Y, Wang J, Liu S, et al. miR-216a promotes breast cancer cell apoptosis by targeting PKCα. Fundam Clin Pharmacol 2019; 33(4): 397-404.
[http://dx.doi.org/10.1111/fcp.12481] [PMID: 31119784]
[37]
Wolf J, Dewi DL, Fredebohm J, et al. A mammosphere formation RNAi screen reveals that ATG4A promotes a breast cancer stem-like phenotype. Breast Cancer Res 2013; 15(6): R109.
[http://dx.doi.org/10.1186/bcr3576] [PMID: 24229464]
[38]
Bortnik S, Choutka C, Horlings HM, et al. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition. Oncotarget 2016; 7(41): 66970-88.
[http://dx.doi.org/10.18632/oncotarget.11408] [PMID: 27556700]
[39]
Zhang X, Li C, Wang D, Chen Q, Li CL, Li HJ. Aberrant methylation of ATG2B, ATG4D, ATG9A and ATG9B CpG island promoter is associated with decreased mRNA expression in sporadic breast carcinoma. Gene 2016; 590(2): 285-92.
[http://dx.doi.org/10.1016/j.gene.2016.05.036] [PMID: 27265029]
[40]
Antonelli M, Strappazzon F, Arisi I, et al. ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy. Oncotarget 2017; 8(13): 21692-709.
[http://dx.doi.org/10.18632/oncotarget.15537] [PMID: 28423511]
[41]
Zhang L, Guo M, Li J, et al. Systems biology-based discovery of a potential Atg4B agonist (Flubendazole) that induces autophagy in breast cancer. Mol Biosyst 2015; 11(11): 2860-6.
[http://dx.doi.org/10.1039/C5MB00466G] [PMID: 26299935]
[42]
Claude-Taupin A, Fonderflick L, Gauthier T, et al. ATG9A Is Overexpressed in Triple Negative Breast Cancer and Its In Vitro Extinction Leads to the Inhibition of Pro-Cancer Phenotypes. Cells 2018; 7(12)e248
[http://dx.doi.org/10.3390/cells7120248] [PMID: 30563263]
[43]
Wang S, Xu Y, Li C, et al. Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by promoting the crosstalk of extrinsic and intrinsic apoptotic signalings. Food Chem Toxicol 2018; 119: 334-41.
[http://dx.doi.org/10.1016/j.fct.2018.02.037] [PMID: 29458160]
[44]
Bagherabad MB, Afzaljavan F, Vahednia E, et al. Association of caspase 8 promoter variants and haplotypes with the risk of breast cancer and its molecular profile in an Iranian population: A case-control study. J Cell Biochem 2019; 120(10): 16435-44.
[http://dx.doi.org/10.1002/jcb.28781] [PMID: 31257627]
[45]
Jiao C, Chen W, Tan X, et al. Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9. J Ethnopharmacol 2020; 247112256
[http://dx.doi.org/10.1016/j.jep.2019.112256] [PMID: 31586690]
[46]
Ren L, Li Y, Zhao Q, et al. miR-519 regulates the proliferation of breast cancer cells via targeting human antigen R. Oncol Lett 2020; 19(2): 1567-76.
[PMID: 31966082]
[47]
Zoeller JJ, Vagodny A, Taneja K, et al. Neutralization of BCL-2/XL enhances the cytotoxicity of T-DM1 in vivo. Mol Cancer Ther 2019; 18(6): 1115-26.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0743] [PMID: 30962322]
[48]
Toupin NP, Arora K, Shrestha P, et al. BODIPY-caged photoactivated inhibitors of cathepsin B flip the light switch on cancer cell apoptosis. ACS Chem Biol 2019; 14(12): 2833-40.
[http://dx.doi.org/10.1021/acschembio.9b00711] [PMID: 31750642]
[49]
Wang Y, Niu H, Hu Z, et al. Targeting the lysosome by an aminomethylated riccardin D triggers DNA damage through cathepsin B-mediated degradation of BRCA1. J Cell Mol Med 2019; 23(3): 1798-812.
[http://dx.doi.org/10.1111/jcmm.14077] [PMID: 30565390]
[50]
Hodgkinson VC. , ELFadl D, Agarwal V, et al. Proteomic identification of predictive biomarkers of resistance to neoadjuvant chemotherapy in luminal breast cancer: a possible role for 14-3-3 theta/tau and tBID? J Proteomics 2012; 75(4): 1276-83.
[http://dx.doi.org/10.1016/j.jprot.2011.11.005] [PMID: 22115752]
[51]
Castelli V, Piroli A, Marinangeli F, et al. Local anesthetics counteract cell proliferation and migration of human triple-negative breast cancer and melanoma cells. J Cell Physiol 2020; 235(4): 3474-84.
[http://dx.doi.org/10.1002/jcp.29236] [PMID: 31541469]
[52]
Menbari MN, Rahimi K, Ahmadi A, et al. miR-483-3p suppresses the proliferation and progression of human triple negative breast cancer cells by targeting the HDAC8>oncogene. J Cell Physiol 2020; 235(3): 2631-42.
[http://dx.doi.org/10.1002/jcp.29167] [PMID: 31508813]

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