Identification of an Alepterolic Acid Derivative as a Potent Anti‐Breast‐Cancer Agent via Inhibition of the Akt/p70^S6K Signaling Pathway

Abstract

Alepterolic acid is a diterpene occurring in the fern Aleuritopteris argentea with potentially biological activity warrant further structural modification. In the present work, sixteen alepterolic acid derivatives were synthesized and evaluated for their anti‐cancer activities. Among them, N‐[m‐(trifluoromethoxy)phenyl] alepterolamide displayed comparable activity (IC50=4.20±0.21 μM) in MCF‐7 cells. Moreover, mechanistic investigations indicated this compound was significantly capable of diminishing cell proliferation and viability of MCF‐7 cells. After treatment with N‐[m‐(trifluoromethoxy)phenyl] alepterolamide, a significant increase in cleaved caspase‐9, cleaved caspase‐3, cleaved poly (ADP‐ribose) polymerase (PARP) and Bax/Bcl2 ratio were observed in MCF‐7 cells, leading to caspase‐dependent apoptotic pathways. Further studies showed this compound promoted cellular apoptosis and inhibited migration in MCF‐7 cells via modulation of Akt/p70S6K signaling pathway. All these results revealed the potential of N‐[m‐(trifluoromethoxy)phenyl] alepterolamide as an appealing therapeutic drug candidate for MCF‐7 breast cancer cells.