Apoptotic activity of fatty acid derivatives may correlate with their inhibition of DNA replication

作者：Miao Chunhui; Du Juan; Dang Hung The; Jeong In Hye; You Song; Park Jang Su; Jung Jee H; Kim Dong Kyoo^*

来源：International Journal of Oncology, 2008, 33(6): 1291-1298.

DOI：10.3892/ijo_00000120

• fatty acid derivatives
• apoptosis
• DNA damage
• DNA replication

The apoptogenic and DNA damaging effects of (E)-10-oxooctadec-8-enoic acid (S5C) and (E)-9-oxooctadec-10-enoic acid (S6C), two structurally related fatty acids isolated from Red Alga Gracilaria verrucosa, were compared and their apoptosis-inducing properties characterized against human lung carcinoma (A549) cells. Significantly, the two acids decreased the rates of proliferation and viability (IC(50) of similar to 170 and similar to 140 mu M) as well as evidence of the induction of apoptosis. Cell morphological changes observed under light microscopy confirmed apoptosis occurrence. The results from Annexin V/PI dual staining and the cell cycle arrest assay indicated that S5C and S6C induced an earlier apoptosis of A549 cells in a concentration-dependent manner. We found that they induced DNA damage and inhibited DNA replication followed by S-phase arrest. In addition. the very sensitive alkaline micro-gel electrophoresis technique (comet assay) was used to estimate the compound-induced DNA single- and double-strand breaks. These findings suggest that S5C and S6C induced A549 cell apoptosis and their effects are associated with DNA damage. Therefore, S5C and S6C have the potential to be developed into anticancer agents due to their relatively easy synthesis and structural manipulation.

• 出版日期2008-12
• 单位沈阳药科大学