Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma cells

• Autorzy: Wolmarans E. , Mqoco T. V. , Stander A. , Nkandeu S. D. , Sippel K. , Mckenna R. , Joubert A.
• Języki publikacji: EN

Abstrakty

EN

Cancer is the second leading cause of death in South Africa. The critical role that microtubules play in cell division makes them an ideal target for the development of chemotherapeutic drugs that prevent the hyperproliferation of cancer cells. The new in silico-designed estradiol analogue 2-ethyl-3-O-sulfamoylestra-1,3,5(10)16-tetraene (ESE-16) was investigated in terms of its in vitro antiproliferative effects on the esophageal carcinoma SNO cell line at a concentration of 0.18 μM and an exposure time of 24 h. Polarization-optical differential interference contrast and triple fluorescent staining (propidium iodide, Hoechst 33342 and acridine orange) revealed a decrease in cell density, metaphase arrest, and the occurrence of apoptotic bodies in the ESE-16-treated cells when compared to relevant controls. Treated cells also showed an increase in the presence of acidic vacuoles and lysosomes, suggesting the occurrence of autophagic processes. Cell death via autophagy was confirmed using the Cyto-ID autophagy detection kit and the aggresome detection assay. Results showed an increase in autophagic vacuole and aggresome formation in ESE-16 treated cells, confirming the induction of cell death via autophagy. Cell cycle progression demonstrated an increase in the sub-G1 fraction (indicative of the presence of apoptosis). In addition, a reduction in mitochondrial membrane potential was also observed, which suggests the involvement of apoptotic cell death induced by ESE-16 via the intrinsic apoptotic pathway. In this study, it was demonstrated that ESE-16 induces cell death via both autophagy and apoptosis in esophageal carcinoma cells. This study paves the way for future investigation into the role of ESE-16 in ex vivo and in vivo studies as a possible anticancer agent.

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2014
• Tom: 19
• Numer: 1
• Opis fizyczny: p.98-115,fig.,ref.

Twórcy

autor

Wolmarans E.

• Department of Physiology, University of Pretoria, South Africa

autor

Mqoco T. V.

• Department of Physiology, University of Pretoria, South Africa

autor

Stander A.

• Department of Physiology, University of Pretoria, South Africa

autor

Nkandeu S. D.

• Department of Physiology, University of Pretoria, South Africa

autor

Sippel K.

• Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA

autor

Mckenna R.

• McKnight Institute, University of Florida, Gainesville, Florida, USA

autor

Joubert A.

• Department of Physiology, University of Pretoria, South Africa

Bibliografia

• 1. Kamangar, F., Dores, G.M. and Anderson, W.F. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J. Clin. Oncol. 24 (2006) 2137–2150.
• 2. Kamangar, F., Chow, W.H., Abnet, C.C. and Dawsey, S.M. Environmental causes of esophageal cancer. Gastroenterol. Clin. North Am. 38 (2009) 27–57.
• 3. Du, B., Zhao, Z., Sun, H., Ma, S., Jin, J. and Zhang, Z. Effects of 2-methoxyestradiol on proliferation, apoptosis and gene expression of cyclin B1 and c-Myc in esophageal carcinoma EC9706 cells. Cell. Biochem. Funct. 30 (2012) 158–165.
• 4. Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E. and Forman, D. Global Cancer Statistics. CA Cancer J. Clin. 61 (2011) 69–90.
• 5. Chu, F.S. and Li, G.Y. Simultaneous occurrence of fumonisin B1 and other mycotoxins in moldy corn collected from the People's Republic of China in regions with high incidences of esophageal cancer. Appl. Environ. Microbiol. 60 (1994) 847–852.
• 6. Myburg, R.B., Dutton, M.F. and Chuturgoon, A.A. Cytotoxicity of fumonisin B1, diethylnitrosamine, and catechol on the SNO esophageal cancer cell line. Environ. Health Perspect. 110 (2002) 813–815.
• 7. Zhou, J. and Giannakakou, P. Targeting microtubules for cancer chemotherapy. Curr. Med. Chem. Anticancer Agents 5 (2005) 65–71.
• 8. Purohit, A., Hejaz, H.A., Walden, L., MacCarthy-Morrogh, L., Packham, G., Potter, B.V. and Reed, M.J. The effect of 2-methoxyoestrone-3-O-sulfamate on the growth of breast cancer cells and induced mammary tumors. Int. J. Cancer 85 (2000) 584–589.
• 9. Chua, Y.S., Chua, Y.L. and Hagen, T. Structure activity analysis of 2-methoxyestradiol analogues reveals targeting of microtubules as the major mechanism of antiproliferative and proapoptotic activity. Mol. Cancer Ther. 9 (2010) 224–235.
• 10. Stander, A., Joubert, F. and Joubert, A. Docking, synthesis, and in vitro evaluation of antimitotic estrone analogs. Chem. Biol. Drug Des. 77 (2011) 173–181.
• 11. Choi, H.J. and Zhu, B.T. Critical role of cyclin B1/Cdc2 up-regulation in the induction of mitotic prometaphase arrest in human breast cancer cells treated with 2-methoxyestradiol. Biochim. Biophys. Acta 1823 (2012) 1306–1315.
• 12. Visagie, M., Mqoco, T. and Joubert, A. Sulphamoylated estradiol analogue induces antiproliferative activity and apoptosis in breast cell lines. Cell. Mol. Biol. Lett. 17 (2012) 549–558.
• 13. Mooberry, S.L. Mechanism of action of 2-methoxyestradiol: new developments. Drug Resist. Updat. 6 (2003) 355–361.
• 14. Zhu, B.T. and Conney, A.H. Is 2-methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis? Cancer Res. 58 (1998) 2269–2277.
• 15. Mabjeesh, N.J., Escuin, D., LaVallee, T.M., Pribluda, V.S., Swartz, G.M., Johnson, M.S., Willard, M.T., Zhong, H., Simons, J.W. and Giannakakou, P. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3 (2003) 363–375.
• 16. Thaver, V., Lottering, M., van Papendorp, D. and Joubert, A. In vitro effects of 2-methoxyestradiol on cell numbers, morphology, cell cycle progression, and apoptosis induction in oesophagealcarcinoma cells. Cell Biochem. Funct. 27 (2009) 205–210.
• 17. Van Zijl, C., Lottering, M.L., Steffens, F. and Joubert, A. In vitro effects of 2-methoxyestradiol on MCF-12A and MCF-7 cell growth, morphology and mitotic spindle formation. Cell Biochem. Funct. 26 (2008) 632–642.
• 18. Voster, C.J.J. and Joubert, A.M. In vitro effects of 2-methoxyestradiol-bissulfamate on the non-tumorigenic MCF-12A cell line. Cell Biochem. Funct. 28 (2010) 412–419.
• 19. Bruce, J.Y., Eickhoff, J., Pili, R., Logan, T., Carducci, M., Arnott, J., Treston, A., Wilding, G. and Liu, G. A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate. Invest. New Drugs 30 (2012) 794–802.
• 20. Harrison, M.R., Hahn, N.M., Pili, R., Oh, W.K., Hammers, H., Sweeney, C., Kim, K., Perlman, S., Arnott, J., Sidor, C., Wilding, G. and Liu, G. A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC). Invest. New Drugs 29 (2011) 1465–1474.
• 21. Tevaarwerk, A.J., Holen, K.D., Alberti, D.B., Sidor, C., Arnott, J., Quon, C., Wilding, G. and Liu, G. Phase I trial of 2-methoxyestradiol NanoCrystal dispersion in advanced solid malignancies. Clin Cancer Res. 15 (2009) 1460–1465.
• 22. Newman, S.P., Ireson, C.R., Tutill, H.J., Day, J.M., Parsons, M.F., Leese, M.P., Potter, B.V.L., Reed, M.J. and Purohit, A. The role of 17beta-hydroxysteroid dehydrogenases in modulating the activity of 2-methoxyestradiol in breast cancer cells. Cancer Res. 66 (2006) 324–330.
• 23. Liu, Q., Jin, W., Zhu, Y., Zhou, J., Lu, M. and Zhang, Q. Synthesis of 3'-methoxy-E-diethylstilbestrol and its analogs as tumor angiogenesis inhibitors. Steroids 77 (2012) 419–423.
• 24. Chiche, J., Ilc, K., Laferriere, J., Trottier, E., Dayan, F., Mazure, N.M., Brahimi-Horn, M.C. and Pouysségur, J. Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. Cancer Res. 69 (2009) 358–368.
• 25. Visagie, M.H. and Joubert, A.M. In vitro effects of 2-methoxyestradiol-bissulfamate on reactive oxygen species and possible apoptosis induction in a breast adenocarcinoma cell line. Cancer Cell Int. 11 (2011) 43–49.
• 26. Supuran, C.T. and Scozzafava, A. Carbonic anhydrases as targets for medicinal chemistry. Bioorg. Med. Chem. 15 (2007) 4336–4350.
• 27. Genis, C., Sippel, K.H., Case, N., Cao, W., Avvaru, B.S., Tartaglia, L.J., Govindasamy, L., Tu, C., Agbandje-McKenna, M., Silverman, D.N., Rosser, C.J. and McKenna, R. Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties. Biochemistry 48 (2009) 1322–1331.
• 28. Stander, B.A., Joubert, F., Tu, C., Sippel, K.H., McKenna, R. and Joubert, A.M. In vitro evaluation of ESE-15-ol, an estradiol analogue with nanomolar antimitotic and carbonic anhydrase inhibitory activity. PLoS One 7 (2012) e52205–e52215.
• 29. Leese, M.P., Leblond, B., Newman, S.P., Purohit, A., Reed, M.J. and Potter, B.V. Anti-cancer activities of novel D-ring modified 2-substituted estrogen-3-Osulfamates. J. Steroid Biochem. Mol. Biol. 94 (2005) 239–251.
• 30. Chander, S.K., Foster, P.A., Leese, M.P., Newman, S.P., Potter, B.V., Purohit, A. and Reed, M.J. In vivo inhibition of angiogenesis by sulfamoylated derivatives of 2-methoxyoestradiol. Br. J. Cancer 96 (2007) 1368–1376.
• 31. Visagie, M.H. and Joubert, A.M. The in vitro effects of 2-methoxyestradiolbis-sulfamate on cell numbers, membrane integrity and cell morphology, and the possible induction of apoptosis and autophagy in a non-tumorigenic breast epithelial cell line. Cell. Mol. Biol. Lett. 15 (2010) 564–581.
• 32. Stander, B.A., Joubert, F., Tu, C., Sippel, K.H., McKenna, R. and Joubert, A.M. Signaling pathways of ESE-16, an antimitotic and anticarbonic anhydrase estradiol analog, in breast cancer cells. PLoS One 8 (2013) e53853–e53871.
• 33. Mqoco, T., Marais, S. and Joubert, A. Influence of estradiol analogue on cell growth, morphology and death in esophageal carcinoma cells. Biocell 34 (2010) 113–120.
• 34. Stander, X.X., Stander, B.A. and Joubert, A.M. In vitro effects of an in silicomodelled 17-beta-estradiol derivative in combination with dichloroacetic acid on MCF-7 and MCF-12A cells. Cell. Prolif. 44 (2011) 567–581.
• 35. Stander, B.A., Marais, S., Vorster, C.J. and Joubert, A.M. In vitro effects of 2-methoxyestradiol on morphology, cell cycle progression, cell death and gene expression changes in the tumorigenic MCF-7 breast epithelial cell line. J. Steroid Biochem. Mol. Biol. 119 (2010) 149–160.
• 36. Kanzawa, T., Kondo, Y., Ito, H., Kondo, S. and Germano, I. Induction of autophagic cell death in malignant glioma cells by arsenic trioxide. Cancer Res. 63 (2003) 2103–2108.
• 37. Knizhnik, A.V., Roos, W.P., Nikolova, T., Quiros, S., Tomaszowski, K.H., Christmann, M. and Kaina, B. Survival and death strategies in glioma cells: autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage. PLoS One 8 (2013) e55665–e55676.
• 38. Moriya, S., Che, X.F., Komatsu, S., Abe, A., Kawaguchi, T., Gotoh, A., Inazu, M., Tomoda, A. and Miyazawa, K. Macrolide antibiotics block autophagy flux and sensitize to bortezomib via endoplasmic reticulum stress-mediated CHOP induction in myeloma cells. Int. J. Oncol. 42 (2013) 1541–1550.
• 39. Taylor, J.P., Tanaka, F., Robitschek, J., Sandoval, C.M., Taye, A., Markovic-Plese, S. and Fischbeck, H. Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum. Mol. Genet. 12 (2003) 749–757.
• 40. Garcia-Mata, R., Gao, Y.S. and Sztul, E. Hassles with taking out the garbage: aggravating aggresomes. Traffic 3 (2002) 388–396.
• 41. Simms-Waldrip, T., Rodriguez-Gonzalez, A., Lin, T., Ikeda, A.K., Fu, C. and Sakamoto, K.M. The aggresome pathway as a target for therapy in hematologic malignancies. Mol. Genet. Metab. 94 (2008) 283–286.
• 42. Nkandeu, D.S., Mqoco, T.V., Visagie, M.H., Stander, B.A., Wolmarans, E., Cronje, M.J. and Joubert, A.M. In vitro changes in mitochondrial potential, aggresome formation and caspase activity by a novel 17-beta-estradiol analogue in breast adenocarcinoma cells. Cell. Biochem. Funct. 31 (2013) 566–574.
• 43. Bialik, S., Zalckvar, E., Ber, Y., Rubinstein, A.D. and Kimchi, A. Systems biology analysis of programmed cell death. Trends Biochem. Sci. 35 (2010) 556–564.
• 44. Pradelli, L.A., Beneteau, M. and Ricci, J.E. Mitochondrial control of caspase-dependent and -independent cell death. Cell. Mol. Life. Sci. 67 (2010) 1589–1597.
• 45. Wang, C. and Klionsky, D.J. The Molecular Mechanism of Autophagy. Mol. Med. 9 (2003) 65–76.
• 46. Tanida, I., Ueno, T. and Kominami, E. LC3 and Autophagy. Methods Mol. Biol. 445 (2008) 77–88.
• 47. Zaarur, N., Meriin, A.B., Gabai, V.L. and Sherman, M.Y. Triggering aggresome formation. Dissecting aggresome-targeting and aggregation signals in synphilin 1. J. Biol. Chem. 283 (2008) 27575–27584.
• 48. Hsieh, Y.C., Athar, M. and Chaudry, I.H. When apoptosis meets autophagy: deciding cell fate after trauma and sepsis. Trends Mol. Med. 15 (2009) 129–138.
• 49. Thorburn, A. Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis 13 (2008) 1–9.
• 50. Maiuri, M.C., Zalckvar, E., Kimchi, A. and Kroemer, G. Self-eating and Self-killing: crosstalk between autophagy and apoptosis. Mol. Cell Biol. 8 (2007) 741–752.