Article Text
Abstract
Introduction/Background Ovarian cancer is one of the fatal cancers in women, often associated with drug resistance. Therefore, finding effective drugs, including naturally derived compounds is urgently needed. We have previously examined the effect of gallic acid (GA) on breast cancer cell line MCF-7 and found a significant anti-cancer activity. We aimed to test the anti-cancer potential of GA monohydrate and six different derivatives of GA on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) human epithelial ovarian cancer cell lines and on HOSE6-3 normal epithelial ovarian cell line. The effect of cisplatin and GA in combination was also examined.
Methodology Cells were exposed to different concentration of GA (0–100 µg/ml), and cisplatin (0–24 µg/ml) and cell viability was tested via AlamarBlue and CCK08 assays. Apoptosis was determined by Hoechst stain.
Results GA monohydrate decreased cell viability in a dose- and time-dependent manner in all cell lines. GA monohydrate was demonstrated to have the highest cytotoxicity to both A2780S and A2780CP cell lines compared to all six derivatives. The highest cytotoxicity of GA was observed in A2780S (IC-50=19.4 µg/ml), followed by A2780CP cells (IC-50=35.6 µg/ml), whereas the least cytotoxicity was observed in HOSE6-3 (IC-59=49.3 µg/ml). Similarly, cisplatin displayed a higher cytotoxicity on A2780S (IC-50=9.4 µg/ml) than on A2780CP (IC-50=23.1 µg/ml). However, cisplatin was more toxic to HOSE6-3 than ovarian cancer cells (IC-50=8.8 µg/ml). There was no significant difference in cytotoxicity between cisplatin and GA either combined or used separately. Apoptosis was estimated to be 49% and 47% in A2780S and A2780CP cell lines respectively at a GA concentration of 25 µg/ml.
Conclusion GA monohydrate exhibited significant cytotoxicity in ovarian cancer cell lines independent of cisplatin, suggesting a cytotoxic effect of GA on ovarian cancer. The growth inhibitory effect of GA, especially on resistant ovarian cancer cells, merits further investigation.
Disclosure We are greatly thankful for His Majesty Sultan Qaboos Trust Fund Grant (SR/MED/MEDE/17/01). Also, we would like to thank Ms Buthaina Al Dhahli for her endless support and help.