Cytotoxic and Apoptotic Effects of Compounds Isolated from Atalantia monophylla Peels on Human Cancer Cell Lines

This study aimed to extract and purify compounds from traditional Thai medicine, A. monophylla peels, and evaluate their antiproliferative and mechanistic effects.

Peels of A. monophylla were extracted using various solvents.  Compounds were isolated using column chromatography and preparative thin-layer chromatography. Structural elucidation was performed using spectroscopic techniques and by comparison with literature data. Antiproliferative activity was assessed using the MTT assay against several human cancer cell lines (MCF-7, HeLa S3, HepG2,HCT116) and normal Vero cells. Apoptosis and cell cycle arrest were evaluated using Hoechst 33342 staining and flow cytometry with annexin V/PI staining.

The acetone extract and its sub-fractions showed potent antiproliferative effects, particularly against MCF-7 breast cancer cells. In contrast, n-hexane and methanol extracts were less active. Bioactivity-guided fractionation yielded two benzoyl tyramine alkaloids: servarine palmitate (1) and acidissiminol epoxide (2), with the latter displaying the highest cytotoxicity. Mechanistic studies revealed hallmark apoptotic features, including membrane blebbing, chromatin condensation, nuclear fragmentation, apoptotic body formation, and loss of adhesion. Additionally, acidissiminol epoxide (2) induced G0/G1 cell cycle arrest, suggesting disruption of DNA synthesis and activation of apoptotic pathways.

This study reports, for the first time, the isolation of tyramine alkaloid 2 from A. monophylla and its potent anticancer activity against breast cancer cells. These findings highlight its potential as a lead compound for the development of novel epoxide-containing anticancer agents.