Discovery of a Pimaradiene that Decreases Viability of MDA‐MB‐468 Cells Through Inhibition of EGFR Signaling Pathway

Abstract

AbstractTriple‐negative breast cancer (TNBC) is characterized by strong invasiveness, high relapse rates, and poor overall survival. It occurs in approximately 15–20 % of all breast cancer cases. Natural compounds are a promising option for managing breast cancer. ent‐8(14),15‐Pimaradiene‐2β,19‐diol (JXE‐23), is a pimaradiene isolated from the fern Aleuritopteris albofusca. However, the effects and molecular mechanisms of JXE‐23 on cancer cells are still unknown. Thus, this study was designed to determine the potential of JXE‐23 for its anticancer properties in TNBC cells. JXE‐23 was evaluated for its antiproliferative activity in vitro against human breast cancer cell lines, and showed selectively cytotoxic activity against MDA‐MB‐468, an EGFR‐overexpressing TNBC cancer cell line, with an IC50 value of 1.17±0.04 μM. Moreover, mechanistic investigations indicated that JXE‐23 was significantly capable of inhibiting cell proliferation and viability in MDA‐MB‐468 cells. In addition, JXE‐23 exerted an anticancer effect against MDA‐MB‐468 cells via restraining cell migration in a dose‐dependent mode. Moreover, after treatment with JXE‐23, the protein expressions of pEGFR, pERK, pAkt and p‐p70S6K were significantly reduced in MDA‐MB‐468 cells. The results underscored that JXE‐23 could be a potential lead compound for the treatment of EGFR‐overexpressing TNBC cells.