Salinomycin inhibits epigenetic modulator EZH2 to enhance death receptors in colon cancer stem cells

References

• Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
   Google Scholar
• De Angelis ML, Francescangeli F, La Torre F, et al. Stem cell plasticity and dormancy in the development of cancer therapy resistance. Front Oncol. 2019;9:626.
   Google Scholar
• Martins-Neves SR, Cleton-Jansen AM, Gomes CMF. Therapy-induced enrichment of cancer stem-like cells in solid human tumors: where do we stand? Pharmacol Res. 2018;137:193–204.
   Google Scholar
• Ganesher A, Chaturvedi P, Sahai R, et al. New Spisulosine Derivative promotes robust autophagic response to cancer cells. Eur J Med Chem. 2020;188:112011.
   Google Scholar
• Tiwari R, Manzar N, Bhatia V, et al. Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer. Nat Commun. 2020;11:384.
   Google Scholar
• Singh AK, Arya RK, Maheshwari S, et al. Tumor heterogeneity and cancer stem cell paradigm: updates in concept, controversies and clinical relevance. Int J Cancer. 2015;136:1991–2000.
   Google Scholar
• Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138:645–659.
   Google Scholar
• Lu D, Choi MY, Yu J, et al. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci U S A. 2011;108(32):13253–13257.
   Google Scholar
• Easwaran H, Tsai HC, Baylin SB. Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol Cell. 2014;54:716–727.
   Google Scholar
• Munoz P, Iliou MS, Esteller M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol. 2012;6:620–636.
   Google Scholar
• Widschwendter M, Fiegl H, Egle D, et al. Epigenetic stem cell signature in cancer. Nat Genet. 2007;39:157–158.
   Google Scholar
• Valk-Lingbeek ME, Bruggeman SW, van Lohuizen M. Stem cells and cancer; the polycomb connection. Cell. 2004;118:409–418.
   Google Scholar
• Francis NJ, Kingston RE, Woodcock CL. Chromatin compaction by a polycomb group protein complex. Science. 2004;306:1574–1577.
   Google Scholar
• Bhatia V, Yadav A, Tiwari R, et al. Epigenetic silencing of miRNA-338-5p and miRNA-421 drives SPINK1-positive prostate cancer. Clin. Cancer Res. 2019;25:2755–2768.
   Google Scholar
• Cao R, Wang L, Wang H, et al. Role of histone H3 lysine 27 methylation in polycomb-group silencing. Science. 2002;298:1039–1043.
   Google Scholar
• Varambally S, Dhanasekaran SM, Zhou M, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–629.
   Google Scholar
• Kleer CG, Cao Q, Varambally S, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 2003;100:11606–11611.
   Google Scholar
• Suva ML, Riggi N, Janiszewska M, et al. EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res. 2009;69:9211–9218.
   Google Scholar
• Deb G, Singh AK, Gupta S. EZH2: not EZHY (easy) to deal. Mol Cancer Res. 2014;12:639–653.
   Google Scholar
• Khanbolooki S, Nawrocki ST, Arumugam T, et al. Nuclear factor-kappaB maintains TRAIL resistance in human pancreatic cancer cells. Mol Cancer Ther. 2006;5:2251–2260.
   Google Scholar
• Zhang Y, Zhang B. TRAIL resistance of breast cancer cells is associated with constitutive endocytosis of death receptors 4 and 5. Mol Cancer Res. 2008;6:1861–1871.
   Google Scholar
• Singh AK, Chauhan SS, Singh SK, et al. Dual targeting of MDM2 with a novel small-molecule inhibitor overcomes TRAIL resistance in cancer. Carcinogenesis. 2016;37:1027–1040.
   Google Scholar
• Fulda S, Debatin KM. Exploiting death receptor signaling pathways for tumor therapy. Biochim Biophys Acta. 2004;1705:27–41.
   Google Scholar
• Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc. 2006;1:1112–1116.
   Google Scholar
• Arya RK, Singh A, Yadav NK, et al. Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis. Sci Rep. 2015;5:18457.
   Google Scholar
• Datta D, Flaxenburg JA, Laxmanan S, et al. Ras-induced modulation of CXCL10 and its receptor splice variant CXCR3-B in MDA-MB-435 and MCF-7 cells: relevance for the development of human breast cancer. Cancer Res. 2006;66:9509–9518.
   Google Scholar
• Maheshwari S, Avula SR, Singh A, et al. Discovery of a novel small-molecule inhibitor that targets PP2A-beta-Catenin signaling and restricts tumor growth and metastasis. Mol Cancer Ther. 2017;16:1791–1805.
   Google Scholar
• Dillies MA, Rau A, Aubert J, et al. A comprehensive evaluation of normalization methods for Illumina high-throughput RNA sequencing data analysis. Brief Bioinform. 2013;14:671–683.
   Google Scholar
• Dewangan J, Srivastava S, Rath SK. Salinomycin: a new paradigm in cancer therapy. Tumour Biol. 2017;39:1010428317695035.
   Google Scholar
• Chaffer CL, Brueckmann I, Scheel C, et al. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci U S A. 2011;108:7950–7955.
   Google Scholar
• Liu X, Yue P, Khuri FR, et al. p53 upregulates death receptor 4 expression through an intronic p53 binding site. Cancer Res. 2004;64:5078–5083.
   Google Scholar
• Takimoto R, El-Deiry WS. Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding site. Oncogene. 2000;19:1735–1743.
   Google Scholar
• Yoshida T, Maeda A, Tani N, et al. Promoter structure and transcription initiation sites of the human death receptor 5/TRAIL-R2 gene. FEBS Lett. 2001;507:381–385.
   Google Scholar
• Martinez-Paniagua MA, Baritaki S, Huerta-Yepez S, et al. Mcl-1 and YY1 inhibition and induction of DR5 by the BH3-mimetic Obatoclax (GX15-070) contribute in the sensitization of B-NHL cells to TRAIL apoptosis. Cell Cycle. 2011;10:2792–2805.
   Google Scholar
• Knutson SK, Kawano S, Minoshima Y, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mole Cancer Therapeut. 2014;13(4):842–854.
   Google Scholar
• Yu J, Cao Q, Yu J, et al. The neuronal repellent SLIT2 is a target for repression by EZH2 in prostate cancer. Oncogene. 2010;29:5370–5380.
   Google Scholar
• Boehmerle W, Muenzfeld H, Springer A, et al. Specific targeting of neurotoxic side effects and pharmacological profile of the novel cancer stem cell drug salinomycin in mice. J Mol Med (Berl). 2014;92:889–900.
   Google Scholar
• Naujokat C, Steinhart R. Salinomycin as a drug for targeting human cancer stem cells. J Biomed Biotechnol. 2012;2012:950658.
   Google Scholar
• Zhi QM, Chen XH, Ji J, et al. Salinomycin can effectively kill ALDH(high) stem-like cells on gastric cancer. Biomed Pharmacother. 2011;65:509–515.
   Google Scholar
• Gupta PB, Fillmore C, Jiang G, et al. Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell. 2011;146:633–644.
   Google Scholar
• Tang DG. Understanding cancer stem cell heterogeneity and plasticity. Cell Res. 2012;22:457–472.
   Google Scholar
• Najumudeen AK, Jaiswal A, Lectez B, et al. Cancer stem cell drugs target K-ras signaling in a stemness context. Oncogene. 2016;35:5248–5262.
   Google Scholar
• Lu Y, Ma W, Mao J, et al. Salinomycin exerts anticancer effects on human breast carcinoma MCF-7 cancer stem cells via modulation of Hedgehog signaling. Chem Biol Interact. 2015;228:100–107.
   Google Scholar
• Huang X, Borgström B, Stegmayr J, et al. The molecular basis for inhibition of stemlike cancer cells by salinomycin. ACS Cent Sci. 2018;4:760–767.
   Google Scholar
• Jangamreddy JR, Ghavami S, Grabarek J, et al. Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells. Biochim Biophys Acta. 2013;1833:2057–2069.
   Google Scholar
• Kim SH, Choi Y-J, Kim K-Y, et al. Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in osteosarcoma U2OS cells. Biochem Biophys Res Commun. 2016;473:607–613.
   Google Scholar
• Boehmerle W, Endres M. Salinomycin induces calpain and cytochrome c-mediated neuronal cell death. Cell Death Dis. 2011;2:e168.
   Google Scholar
• Verdoodt B, Vogt M, Schmitz I, et al. Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. PLoS One. 2012;7:e44132.
   Google Scholar
• Mai TT, Hamaï A, Hienzsch A, et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem. 2017;9(10):1025–1033.
   Google Scholar
• Heijmans J, van Lidth de Jeude J, Koo B-K, et al. ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response. Cell Rep. 2013;3:1128–1139.
   Google Scholar
• Wielenga MCB, Colak S, Heijmans J, et al. ER-stress-induced differentiation sensitizes colon cancer stem cells to chemotherapy. Cell Rep. 2015;13:489–494.
   Google Scholar
• Feng YX, Sokol ES, Del Vecchio CA, et al. Epithelial-to-mesenchymal transition activates PERK-eIF2alpha and sensitizes cells to endoplasmic reticulum stress. Cancer Discov. 2014;4:702–715.
   Google Scholar
• Mekahli D, Bultynck G, Parys JB, et al. Endoplasmic-reticulum calcium depletion and disease. Cold Spring Harb Perspect Biol. 2011;3:a004317-a004317.
   Google Scholar
• Todaro M, Alea MP, Di Stefano AB, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007;1:389–402.
   Google Scholar
• Calzolari A, Saulle E, De Angelis ML, et al. Salinomycin potentiates the cytotoxic effects of TRAIL on glioblastoma cell lines. PLoS One. 2014;9:e94438.
   Google Scholar
• Parajuli B, Shin SJ, Kwon SH, et al. Salinomycin induces apoptosis via death receptor-5 up-regulation in cisplatin-resistant ovarian cancer cells. Anticancer Res. 2013;33:1457–1462.
   Google Scholar
• Benoit YD, Laursen KB, Witherspoon MS, et al. Inhibition of PRC2 histone methyltransferase activity increases TRAIL-mediated apoptosis sensitivity in human colon cancer cells. J Cell Physiol. 2013;228:764–772.
   Google Scholar
• Elias A, Siegelin MD, Steinmuller A, et al. Epigenetic silencing of death receptor 4 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in gliomas. Clin Cancer Res. 2009;15:5457–5465.
   Google Scholar
• Yang SZ, Xu F, Zhou T, et al. The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand. J Biol Chem. 2017;292:10390–10397.
   Google Scholar
• Hu S, Yu L, Li Z, et al. Overexpression of EZH2 contributes to acquired cisplatin resistance in ovarian cancer cells in vitro and in vivo. Cancer Biol Ther. 2010;10:788–795.
   Google Scholar
• van Vlerken LE, Kiefer CM, Morehouse C, et al. EZH2 is required for breast and pancreatic cancer stem cell maintenance and can be used as a functional cancer stem cell reporter. Stem Cells Transl Med. 2013;2:43–52.
   Google Scholar
• Rizzo S, Hersey JM, Mellor P, et al. Ovarian cancer stem cell-like side populations are enriched following chemotherapy and overexpress EZH2. Mol Cancer Ther. 2011;10:325–335.
   Google Scholar
• Adhikary G, Grun D, Balasubramanian S, et al. Survival of skin cancer stem cells requires the Ezh2 polycomb group protein. Carcinogenesis. 2015;36:800–810.
   Google Scholar
• Kim KH, Roberts CW. Targeting EZH2 in cancer. Nat Med. 2016;22:128–134.
   Google Scholar