O9 Isolation, identification and anti-cancer activity of minor alkaloids from Triclisia subcordata Oliv

Abstract

Triclisia subcordata Oliv (Menispermeaceae) is an African medicinal plant traditionally used for the treatment of various diseases, including cancer. This study aimed to isolate and identify minor alkaloids present in this plant and assay their anticancer activities. Isochondodendrine (1) and 2’-norcocsuline (2) as two minor alkaloids together with the abundant cycleanine (3) [1] were isolated and identified by mass spectrometry and nuclear magnetic resonance spectroscopy. Both isochondodendrine and 2’-norcocsuline exhibited potent in vitro cytotoxicity in four ovarian cancer cell lines (A2780, Igrov-1, Ovcar-8, and Ovcar-4) with an IC 50 range of 3.5–17 μM and 0.8–2.9 μM (assessed via sulforhodamine B dye assay), respectively. The IC 50 in cell growth assays using normal human ovarian epithelial cells were 10.5 ± 1.2 μM and 8.0 ± 0.2 μM for isochondodendrine and 2’-norcocsuline, respectively. These alkaloids showed greater potencies for the cancer cells compared to normal cells. Apoptosis induction by these alkaloids was studied by caspase activity assay, western blot, and flow cytometry. They induced apoptosis in ovarian cancer cells by activation of caspases 3/7, cleavage of PARP, an increase in subG1 cell cycle phase and increases in both early and late apoptotic cells. Therefore isochondodendrine and 2’-norcocsuline are among the least abundant in T. subcordata, which also contribute to its cytotoxic activity and can be potential hit compounds for future development for the treatment of ovarian cancer.