Abstract: Objective: To investigate the anti-tumor activity of mitissimol D, a novel sesquiterpene compound extracted from Lactarius vellereus, and its effects on cell cycle and apoptosis. Methods: 3-(4,5)-Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay was used to determine the inhibitory effect of mitissimol D on the proliferation of A549, HCT-8, Bel-7402, SMMC7721 and HeLa cells and to determine the half maximal inhibition concentration (IC50) in comparison with cisplatin as a positive control. A549 cells sensitive to mitissimol D were selected to observe the morphological changes and the changes in cell apoptosis rate and cell cycle. Results: Mitissimol D could effectively inhibit the proliferation of A549, Bel-7402, SMMC7721 and HeLa cells with IC50 (72 h) of 2.46, 19.09, 18.21 and 17.05 μg/mL, respectively. Mitissimol D could cause significant morphological changes of A549 cells, leading to the formation of apoptosomes and it also could induce apoptosis in A549 cells ( 32.14% apoptosis rate at 100 μg/mL after 72 h) and lead to cell block in the S phase. Conclusion: Mitissimol D can significantly inhibit the proliferation of tumor cells from a variety of tissue sources, of which A549 cells are the most sensitive, by interfering with the cell cycle. These findings provide an experimental basis for the development of mitissimol D as a new sesquiterpene compound.

Key words: Lactarius vellereus, mitissimol D, anti-tumor activity, apoptosis, cell cycle