In vitro cytotoxicity of salvicine, a novel diterpenoid quinone

AIM: To study the in vitro cytotoxicity of 4,5-seco-5,10-friedo-abieta-3,4- dihydroxy-5(10),6,8,13-tetraene-11,12-dione (salvicine), a novel diterpenoi d quinone compound on human tumor cell Lines and its effect on cell cycle p rogression. METHODS: Growth inhibition of human tumor cells was measured by microculture tetrazolium assay (MTT). Cell cycle was analyzed by flow cyto metry. RESULTS: Exposing tumor cell lines tested to salvicine for 72 h, in comparison with reference drugs vincristine (VCR) and etoposide (VP-16), sa lvicine was as cytotoxic as VP-16 and weaker than VCR in 3 leukemia cell li nes. For 12 solid tumor cell lines, salvicine exhibited cytotoxic activitie s and was over 5.41- and 4.15-fold stronger than VCR and VP-16, respectivel y. Salvicine presented better activities especially against gastric and lun g carcinoma cell lines. Exposing K562 leukemia cells to 9 graded concentrat ions of salvicine (from 0.39 to 100 mu mol.L-1) for 24 h and to salvicine 1 0 mu mol.L-1 for 7 different periods (from 1 to 48 h), the growth inhibitio n of cells was enhanced along with increased concentration or prolonged exp osure. Cell cycle analysis demonstrated that salvicine arrested K562 cells in 1 phase and this effect was also heightened with increased concentration or extended exposure. CONCLUSION: Salvicine exhibited potent cytotoxic act ivities against various human tumor cell lines, and blocked K562 leukemia c ells in G(1) phase of cell cycle.