In vitro and in vivo antitumor effects of the diterpene-enriched extract from Taxodium ascendens through the mitochondrial-dependent apoptosis pathway

Extracts and components of Taxodium ascendens Brongn, an excellent afforestation tree, have exhibited several activities, including antibacterial activity and inhibitory activity on carbonic anhydrase II. However, the anti-hepatocellular carcinoma (anti-HCC) activity of extracts from the leaves of T. ascendens (TALE) remains unclear. In the present study, six diterpenoid compounds were isolated from a TALE extract. Here, the pro-apoptotic activities and the molecular mechanisms of TALE and the compounds 1-6 on HepG2 and Hep3B HCC cells were evaluated. Results show that the TALE and compounds 1-6 were able to induce apoptosis in the HepG2 and Hep3B HCC cells, particularly ferruginol (3). Mechanistically, the application of TALE and ferruginol (3) resulted in a significant decrease in mitochondria membrane potential, which was coupled with an increase in the Bax/Bcl-2 ratio and caspase-3/-9 activity. In vivo experiments showed that oral administration of TALE inhibited the proliferation of transplanted H22 cells in Kunming mice. However, TALE toxicity in KM mice was undetectable. The study provides strong evidence for the anti-HCC capacity of TALE.