In vitro cytotoxicity of salvicine, a novel diterpenoid quinone.

Abstract

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 diterpenoid quinone compound on human tumor cell lines and its effect on cell cycle progression.

Methods: Growth inhibition of human tumor cells was measured by microculture tetrazolium assay (MTT). Cell cycle was analyzed by flow cytometry.

Results: Exposing tumor cell lines tested to salvicine for 72 h, in comparison with reference drugs vincristine (VCR) and etoposide (VP-16), salvicine was as cytotoxic as VP-16 and weaker than VCR in 3 leukemia cell lines. For 12 solid tumor cell lines, salvicine exhibited cytotoxic activities and was over 5.41- and 4.15-fold stronger than VCR and VP-16, respectively. Salvicine presented better activities especially against gastric and lung carcinoma cell lines. Exposing K562 leukemia cells to 9 graded concentrations of salvicine (from 0.39 to 100 mumol.L-1) for 24 h and to salvicine 10 mumol.L-1 for 7 different periods (from 1 to 48 h), the growth inhibition of cells was enhanced along with increased concentration or prolonged exposure. Cell cycle analysis demonstrated that salvicine arrested K562 cells in G1 phase and this effect was also heightened with increased concentration or extended exposure.

Conclusion: Salvicine exhibited potent cytotoxic activities against various human tumor cell lines, and blocked K562 leukemia cells in G1 phase of cell cycle.