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Flavonoids from Vitex trifolia L. inhibit cell cycle progression at G 2 /M phase and induce apoptosis in mammalian cancer cells

2005; Taylor & Francis; Volume: 7; Issue: 4 Linguagem: Inglês

10.1080/10286020310001625085

1477-2213

Wenxin Li, Cheng‐Bin Cui, Bing Cai, Haiyan Wang, Xin‐Sheng Yao,

Traditional Chinese Medicine Analysis

Six flavonoids, persicogenin (1), artemetin (2), luteolin (3), penduletin (4), vitexicarpin (5) and chrysosplenol-D (6), have been isolated for the first time as new cell cycle inhibitors from Vitex trifolia L., a Chinese folk medicine used to treat cancers, through a bioassay-guided separation procedure. They were identified by spectroscopic methods. The inhibitory effects of 1–6 on the proliferation of mammalian cancer cells have been evaluated by the SRB (sulforhodamine B) method and their effects on cell cycle and apoptosis investigated by flow cytometry with the morphological observation under light microscope and by agarose-gel electrophoresis to detect internucleosomal DNA fragmentation. Compounds 1–6 inhibited the proliferation of mouse tsFT210 cancer cells with the IC50s (μg ml−1) > 100 (inhibition rate at 100 μg ml−1, 47.9%) for 1, >100 (inhibition rate at 100 μg ml−1, 49.6 %) for 2, 10.7 for 3, 19.8 for 4, 0.3 for 5, and 3.5 for 6. Flow cytometric investigations for 1–6 demonstrated that 1–5 mainly inhibited cell cycle at the G2/M phase in a dose-dependent manner with a weak induction of apoptosis on the tsFT210 cells, while 6 induced mainly apoptosis of the same tsFT210 cells also in a dose-dependent manner together with a weak inhibition of the cell cycle at the G0/G1 and G2/M phases, demonstrating that 1–6 exert their anti-proliferative effect on tsFT210 cells through inhibiting cell cycle and inducing apoptosis. In contrast to the cell cycle G2/M phase inhibitory main effect on tsFT210 cells, 5 induced mainly apoptosis on human myeloid leukemia K562 cells with a weak inhibition of the cell cycle at the G2/M phase. The present result provides flavonoids 1–6 as new cell cycle inhibitors and 1 and 4 as new anticancer flavonoids, which not only provide the first example of cell cycle G2/M phase inhibitory and apoptosis-inducing constituents of V. trifolia L. but also explain the use of Vitex trifolia L. by Chinese people to treat cancers.