Anti-proliferative and apoptosis-inducible activity of labdane and abietane diterpenoids from the pulp of Torreya nucifera in HeLa cells.

Two abietane and one labdane type diterpenoids were isolated from the methanol extracts of Torreya nucifera pulp and investigated for their ability to inhibit the growth of human cancer cells. Among the three compounds, the labdane compound kayadiol was found to have the most effective inhibitory effect against a wide variety of human cancer cells. Using the MTT assay, kayadiol was determined to have an IC50 (50% inhibition concentration) of 30 µM in HeLa cells, and also to exhibit anti-proliferative effects towards six other human cancer cell lines, with IC50 values of 30-50 µM. Kayadiol treatment of HeLa cells resulted in a dose-dependent generation of apoptotic events, including DNA laddering (≤100 µM). Moreover, kayadiol-treated HeLa cells showed activation of caspases-3 and -9, as well as an increase in the depolarization of mitochondrial membrane potential and the Bax/Bcl-2 ratio. These results indicate that a mitochondria-related apoptotic pathway is involved in the kayadiol-induced death of HeLa cells. Kayadiol is therefore a promising novel anti-proliferative agent and merits further investigation.