Anti-lung cancer activity of lotusine in non-small cell lung cancer HCC827 via reducing proliferation, oxidative stress, induction of apoptosis, and G0/G1 cell cycle arrest via suppressing EGFR-Akt-ERK signalling.

Abstract

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide, with resistance to targeted therapies and the need for novel therapeutic agents driving ongoing research. In this study, we investigated the anti-lung cancer activity of lotusine, a natural alkaloid, in the A549 (non-EGFR mutant), and EGFR-mutant HCC827 NSCLC cell line (deletion in exon 19). Our results demonstrated that lotusine significantly inhibited cell proliferation in a concentration- and time-dependent manner of HCC827 cells in comparison to A549 cells. Mechanistic analysis revealed that lotusine induced apoptosis in HCC827 cells, as evidenced by increased expression of pro-apoptotic markers (Bax and cleaved caspase-3) and decreased levels of anti-apoptotic proteins (Bcl-2). Cell cycle analysis indicated that lotusine caused G0/G1 phase arrest. Importantly, lotusine exerted its effects through the inhibition of the epidermal growth factor receptor (EGFR) EGFR-Akt-ERK signaling pathway, as evidenced by reduction of p-EGFR, p-Akt, and p-ERK in a western blot analysis in HCC827 cells. These findings suggest that lotusine exerts potent anti-cancer effects via a multifaceted mechanism, including inhibition of proliferation, apoptosis induction, and cell cycle arrest, predominantly mediated by EGFR suppression. This study highlights lotusine as a promising therapeutic candidate for the treatment of EGFR-mutant NSCLC and provides insights into its molecular mechanisms of action, paving the way for further preclinical and clinical evaluations.