Labdane-type diterpenes as new cell cycle inhibitors and apoptosis inducers from Vitex trifolia L.
Five labdane-type diterpenes, vitexilactone (1), (rel 5S,6R,8R,9R,10S)-6-acetoxy-9-hydroxy-13(14)-labden-16,15-olide (2), rotundifuran (3), vitetrifolin D (4), and vitetrifolin E (5), have been isolated from Vitex trifolia L., a Chinese folk medicine used to treat cancers, as new cell cycle inhibitors and apoptosis inducers through a bioassay-guided separation procedure and were identified by spectroscopic methods. Compounds 1-5 dramatically induced apoptosis both on tsFT210 and K562 cells at higher concentrations while at lower concentrations they inhibited the cell cycle progression of both tsFT210 and K562 cells at the G0/G1 phase. MIC values for 1-5 for inducing apoptosis and concentration regions for 1-5 for inhibiting cell cycle both on tsFT210 and K562 cells have also been determined. Furthermore, the inhibitory effects of 1-5 on the proliferation of tsFT210 and K562 cells have been evaluated by MTT assay to obtain IC50 values to confirm that 1-5 are anticancer components of Vitex trifolia L., which exert their anti-proliferative effect on cancer cells through inducing apoptosis and inhibiting the cell cycle. The present results provide labdane-type diterpenes, 1-5, as a new class of cell cycle inhibitors and compounds 1, 2, 4, and 5 as new apoptosis inducers, which also explains, for the first time, the usage of Vitex trifolia L. by Chinese people to treat cancers.
Li
Wen-Xin
WX
Tianjin Institute for Biomedical Research (TIBiR), Tianjin 300384, China.
Cui
Cheng-Bin
CB
Cai
Bing
B
Yao
Xin-Sheng
XS
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005638:Fruit / Q000737:chemistry; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008826:Microbial Sensitivity Tests; D020950:Vitex / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes