Tautomeric phytosterols from Vernonia amygdalina Delile and their anti-cervical cancer activity

Vernonia amygdalina Delile is generally used as green vegetables for cuisine in Nigeria and health tea or products in southeast of china. It was also used as folk medicine for the treatment of anti-helminth, febrifuge, digestive tonic and wounds. In this study, eleven undescribed phytosterols (1-2, 4-12) and six known analogues (3, 13-17) were isolated from the stems of V. amygdalina. Their structures including absolute configurations were elucidated by comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS), X-ray diffraction and com-parison of their ECD spectra. Besides, the tautomerism of phytosterols (1, 3-6, 12-17) with hemiacetal moiety were analyzed by solution NMR with different deuterated solvent and variable-temperature experiments. In addition, the cytotoxic activities of isolates against HeLa cells were evaluated. As a result, compound 10 exhibited the most potent anti-cervical cancer activity with the IC50 of 22.44 mu M. Mechanism studies indicated that 10 triggered HeLa cells apoptosis through activating caspase signaling pathway. Furthermore, 10 could arrest the cell cycle in S phase and suppress the activation of the PI3K/AKT/mTOR pathway, leading to the inhibition of HeLa cells proliferation.

Automated summary

This study identified new phytosterols from Vernonia amygdalina and evaluated their cytotoxic activities against HeLa cervical cancer cells. Compound 10 exhibited the most potent anti-cancer activity, inducing apoptosis in HeLa cells through caspase signaling pathway activation and cell cycle arrest in S phase.