Molecular insights into induction of apoptosis and regulation of cell cycle proliferation by cycloartane triterpenoids from Dysoxylum malabaricum in breast cancer cells.

Cycloartane triterpenoids (CATT), natural compounds derived from Dysoxylum malabaricum, have substantiated promising anticancer potential, specifically against breast adenocarcinoma T-47D cells. However, the underlying mechanisms of action remain largely unexplored. The present work investigated the antiproliferative and pro-apoptotic effects of CATT on human breast cancer cells both in vitro and in vivo. CATT exhibited potent cytotoxicity against T-47D cells (IC50 = 40 µg/ml) while sparing normal cells (IC50 > 80 µg/ml). CATT treatment significantly suppresses the growth of breast cancer cells through G2/M phase cell cycle arrest, which was accompanied by decreased expression of cyclin B1. Interestingly, CATT increases intracellular reactive oxygen species (ROS) levels by disrupting mitochondrial dynamics, contributing to apoptosis induction. Further mechanistic studies revealed that increased levels of cleaved PARP-1, Bax, Cytochrome c, cleaved caspase-9 and cleaved caspase-3, along with decreased levels of PCNA, mutated p53 and Bcl-2, confirm mitochondrial-mediated cell death. Intriguingly, in vivo studies on Balb/c mice bearing T-cell lymphoma further supported these findings, showing extended lifespan, reduced tumour burden and restoring normal histoarchitecture. Importantly, molecular docking results corroborated the in vitro data by demonstrating direct interactions with apoptotic proteins and support the proposed apoptotic mechanism. In conclusion, CATT induces apoptosis in breast adenocarcinoma T-47D cells through mitochondrial dysfunction and caspase activation, and demonstrates potent antitumor activity both in vitro and in vivo. These findings highlight the potential of CATT as a promising natural compound for the development of novel breast cancer therapeutics. Schematic diagram of underlying anticancer mechanism induced by CATT in breast adenocarcinoma.