Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma cells

Cellular & Molecular Biology Letters

Robert McKenna²  Andre Stander¹  Sandra D. Nkandeu¹  Annie Joubert¹  Elize Wolmarans¹  Katherine Sippel³  Thandi V. Mqoco¹ 

[1] Department of Physiology, University of Pretoria, Pretoria, South Africa$$;McKnight Institute, University of Florida, Gainesville, USA$$;Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, USA$$

关键词: Antiproliferative;    ESE-16;    Esophageal carcinoma;    In vitro;    Apoptosis;    Autophagy;   

DOI  :  10.2478/s11658-014-0183-7

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

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.

【 授权许可】

Unknown