Synergistic enhancement of the antitumor activity of 5-fluorouracil by bornyl acetate in SGC-7901 human gastric cancer cells and the determination of the underlying mechanism of action.

OBJECTIVE

To investigate the anticancer activity of bornyl acetate and its combination with low dose 5-fluorouracil (5-FU) in human gastric cancer (SGC-7901) cells and to evaluate their effects on cell cycle, apoptosis, cancer cell morphology and DNA fragmentation.

METHODS

The anticancer activity of bornyl acetate, 5-FU and their combination against human gastric cancer (SGC-7901) cells was evaluated by MTT assay. Flow cytometry using propidium iodide (PI) as a staining agent was used to study the effect of the extract on cell cycle phase distribution. Apoptosis induced by bornyl acetate and 5-FU was evaluated by Annexin V binding assay using flow cytometer. Alterations in cell morphology following apoptosis was studied by fluorescence microscopy as well as transmission electron microscopy.

RESULTS

Bornyl acetate induced dose-dependent growth inhibitory effects on human gastric cancer cells in vitro.The combination of bornyl acetate with 5-FU induced a much more growth inhibitory effect on these cells indicating a synergistic enhancement of anticancer activity of 5-FU. The combined effect of bornyl acetate and 5-FU also resulted in greater apoptosis induction as well as cell cycle arrest in comparison to the individual treatment by bornyl acetate or 5-FU. Fluorescence microscopy as well as transmission electron microscopy also revealed that the combination of bornyl acetate with 5-FU resulted in greater apoptosis induction as well as cell morphology alterations. The percentages of early as well as late apoptotic cells were much higher in the combination treatment in comparison to separate treatment by bornyl acetate or 5-FU.

CONCLUSIONS

Bornyl acetate potentiates the anticancer activity of 5-FU in human gastric cancer (SGC-7901) cells by inducing apoptosis, DNA fragmentation as well as G2/M cell cycle arrest.