The Effect Of Four Diterpenoids On Tumor Cell Proliferation And Angiogenesis In Vitro

OBJECTIVES:In this study,fourditerpenoid compounds(Sh-l,Sh-2,Sxx-l,ER-B) whose molecular weight is in range of 344-432 were isolated. Their activities on human tumor cells proliferation and angiogenesis were assayed in vitro in order to find new anti-tumor drug. METHODS: The cytotoxicity of four diterpenoids in seven human tumor cell lines (K562,SGC-7901,BIU,TYK,Hela,CNE and MNK-28) was measured by modified MTT or SRB assay. Their effects on angiogenesis in vitro were measured by the proliferation, migration and tube formation assay using ECV304 (human umbilical vein endothelial cell). RESULTS: Four diterpenoids exhibited cytotoxicity in seven human tumor cell lines tested. The IC50 of Sh-1 for seven human tumor cell lines was less than 12.74ug/ml(3.50X 10"5M).The IC50 of Sh-2 for K562,SGC-7901,Hela and MNK-28 was less than 7.42ug/ml(2.05 X 10'5M).The IC50 of Sxx-1 for K562,Hela,BIU,TYK,MNK-28 and CNE was less than 16.01ug/ml(3.71 X 10-5M). The IC50 of ER-B for six tumor cell lines(K562, SGC-7901 , BIIK TYK, Hela, CNE) was less than 8.20ug/ml(2.38X 10"5M). Sh-1, Sh, Sxx-1, ER-B have inhibitory effect on the proliferation of ECV304 and the IC50 for ECV304 was between 6.38 - 12.95μg/ml(1.47 X 10-5- 3.76 X 10-5M) Four diterpenoids have different effects on the migration of ECV304 and their IC50 was 0.29 ~ 1.97μg/ml(8.01 X 10-7-5.41 X l0-6M)Besides, Sxx-1, ER-B can stimulate the migration of ECV304 at the concentrations between 1.23X10-7~3.70X 10-7M.Four diterpenoids have all inhibition on tube formation with IC50 being between 0.19-1.21μg/ml(4.25 X 10-7-2.80X 10-6M). CONCLUSIONS:Four diterpenoids were shown to have different inhibitory effect on several human tumor cells in vitro.They could inhibit the migration, tube formation of ECV304 at some concentrations where they had no effect on the proliferation of ECV304.