Chapter 14 - Small Molecule–Mediated Simultaneous Induction of Apoptosis and Autophagy

Abstract

Cell proliferation, differentiation, and death are the three vital processes for maintenance of cell homeostasis. Apoptosis and autophagy are the two key programmed cell death pathways that act in a cell, without affecting the neighboring cells and play roles not only in development and morphogenesis but also in various diseases such as diabetes, cardiovascular diseases, infectious diseases, and cancer. Breast cancer is the leading cancer type in female populations that needs to be prevented or treated. Nowadays several treatments are available for treating breast cancer. Among them targeted chemotherapy plays a crucial role. The drugs available for breast cancer may act in two different ways either by decreasing cell proliferative pathways or by increasing cell death pathways in cancer cells. These drugs mainly target three important hormone receptors (estrogen, progesterone, Her2) whose levels are high in breast cancer especially at primary stage. ESC8 is one such drug that is designed to target estrogen receptor, but the results were astonishing as it showed its action not only on estrogen receptor (ER)-positive cells but also on ER-negative cell lines. Though the exact mechanism of action of ESC8 is not well understood, the results show that ESC8 acts through downregulation of mTOR protein levels via PI3k-AKT-mTOR signaling pathway, which is activated in most of the cancers and is probably one of the targets of ESC8. Simultaneously, ESC8 activates autophagy as well as apoptosis. This rare, dual phenomenon is observed only in a few available drug targets. Though results have shown that ESC8 mediates its action through downregulation of mTOR and upregulation of cell death pathways, with autophagic upregulation, further experiments need to be performed to explore the exact cytotoxic mechanism mediated by ESC8. It will be helpful for furthering translational aspect of this interesting molecule.