Investigating the Effects of Thiostrepton on Apoptotic Cell Death in C. elegans

Abstract

Thio has been drawing increasing attention for its potent antibacterial activity and, more importantly, for its recently identified tumoricidal effect on cancer cells in vitro. It has been reported that Thio can inhibit cancer cells' proliferation and tumor growth and induce apoptosis in various cancer cell lines. However, the in vivo anti-tumor effect of Thio requires further exploration. In this study, we used Caenorhabditis elegans (C. elegans) as an in vivo model system to explore the impact of Thio on inducing programmed cell death. To this end, we have utilized various C. elegans apoptotic mutants to functionally characterize the effect of Thio in different types of apoptosis. Furthermore, the DNA damage response upon Thio treatment was examined by staining the isolated germline using a specific antibody. Also, Thio’s oxidative stress induction was monitored by analyzing the induction of various stress markers. Importantly, this study suggests that Thio triggers apoptosis via a CED-3/Caspase and CED-4/Apaf-1-dependent and CEP-1/P53 and EGL-1/BH-only protein-independent pathways, indicating that, in contrast to the reported in vitro cell culture system, thus, Thio induces apoptosis through the core apoptotic machinery in C. elegans in the level of CED-9/Bcl-2. Furthermore, we unlinked the apoptotic-inducing effect of Thio to the generation of the radical oxygen species previously reported in the various cell types. All in all, this study reflects the significance of Thio in inducing apoptosis. It provides a comprehensive overview of its mechanisms of action at the organismal level, laying the groundwork for further investigations.

Date of Award	2024
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences