New Cytotoxic Sesquiterpene Lactones from the Leaves of Tithonia Diversifolia and their Apoptosis Effect Evaluation in KB Cancer Cells.

ABSTRACT

From the leaves of Tithonia diversifolia, nine sesquiterpenoids (1-9), including two new ones (tagitinin J (1) and tagitinin K (2)) were isolated and structurally determined. Their chemical structures were elucidated by extensive analyses of the HRESIMS and NMR spectral data, as well as comparison with the literature. All of the isolated compounds (except compounds 7-9) significantly exhibited cytotoxic activity against four human cancer cell lines (KB, HepG2, A549 and MCF7), with IC50 values ranging from 0.29-17.0 µM, which were in the same range as the positive control ellipticine or even lower. Further, the apoptosis induction effects of two new compounds 1 and 2 were also investigated and reported. While compound 2 did not induce the apoptosis in KB cells at test concentrations, compound 1 was found to possess anti-proliferative activity through concentration-dependently inducing cell cycle arrest at S phase, morphological changes, activation of caspase 3, and an increase in the early-stage apoptosis of KB cells at a concentration of 7.26 µM.