Anastasis induced by bee venom in normal cells compared to persistent cell death in breast cancer cells

Abstract

Anastasis is a phenomenon that has been recently defined as a return from induced apoptosis. Its mechanism has not been clearly elucidated. Anastasis is thought to be involved in the development of drug resistance in cancer cells, however the distinct regulation of anastasis in normal and cancerous cells during anti-cancer therapy has not been discovered. One of the most privileged therapy strategies focuses on the drugs that are selectively cytotoxic in cancer cells but not negatively affect normal cell proliferation. This study for the first time comparatively evaluated the anastatic effect of a common synthetic cytotoxic agent, cisplatin and a natural cytotoxic agent, bee venom. The study showed that bee venom induced anastasis in normal cells (MCF10A, NIH3T3 and ARPE19) but cancer cells (MDA-MB-231 and MCF7) were irreversibly in cell death process. Liver cancer cells (HEPG2) were more resistant to bee venom-induced persistent cell death and tended to recover at higher concentrations compared to breast cancer cells. However, cisplatin induced persistent cell death in both normal and cancerous cells. Besides, selectivity indexes of bee venom in terms of IC50 values were higher than cisplatin. This study indicates that bee venom produces such an effect by selectively inducing anastasis only in normal cells suggesting that bee venom has prominent potential for cancer therapy, in particular for breast cancer, with recovery and maintenance of normal cells viability. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/579605v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@4ba438org.highwire.dtl.DTLVardef@a7982org.highwire.dtl.DTLVardef@1af5950org.highwire.dtl.DTLVardef@110d199_HPS_FORMAT_FIGEXP M_FIG C_FIG