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Addition of Gallic Acid Overcomes Resistance to Cisplatin in Ovarian Cancer Cell Lines
Najwa Al Balushi1, Syed Imran Hassan2, Nada Abdullah1
1Department of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, P. O. Box 35, PC 123, AlKhoud, Muscat, Oman.
Objective:
Ovarian cancer is one of the leading causes of cancer-related mortality in women, and is often associated with drug resistance. Therefore, finding effective drugs, including naturally derived compounds, is urgently needed. Herein, we aimed to test the anti-cancer potential of gallic acid monohydrate (GA) and its congeners on cisplatin-sensitive (A2780S), and resistant (A2780CP) ovarian cancer and normal ovarian (HOSE6-3) cell lines.
Methods:
Cytotoxicity was assessed by AlamarBlue and CCK08 assays by exposing cells to different concentrations of cisplatin (0-21µg/mL), GA and its congeners (0-100µg/mL), and a combination of GA and cisplatin. Apoptosis was estimated by Hoechst stain and monitoring the relative RNA expression of the apoptotic effector caspase-3 using qRT-PCR.
Results:
GA decreased cell viability in a concentration-dependent manner in all cell lines, with an IC50 of 19.39µg/mL (A2780S), 35.59 µg/mL (A2780CP), and 49.32µg/mL (HOSE6-3). GA displayed higher cytotoxicity than its congeners. An apoptotic rate estimation of approximately 20% and 30% was obtained in A2780S and A2780CP. While the cytotoxicity observed with cisplatin and GA was comparable, combining the two enhanced the cytotoxicity significantly, especially in the A2780CP cell line (p<0.05).
Conclusion:
These data suggest that GA may help overcome the resistance. Hence, the cytotoxic effects of GA, especially on chemo-resistant ovarian cancer cells merit further investigation.
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Insights
Gallic acid monohydrate (GA) shows potent anti-cancer effects against ovarian cancer cells, including drug-resistant types. Combining GA with cisplatin enhances cytotoxicity, suggesting potential for overcoming chemoresistance.
Area of Science:
- Oncology
- Natural Product Chemistry
- Molecular Biology
Background:
- Ovarian cancer is a leading cause of cancer mortality in women.
- Drug resistance is a major challenge in ovarian cancer treatment.
- Naturally derived compounds offer potential therapeutic avenues.
Purpose of the Study:
- To evaluate the anti-cancer potential of gallic acid monohydrate (GA) and its related compounds.
- To assess the efficacy of GA against cisplatin-sensitive and resistant ovarian cancer cell lines.
- To investigate the synergistic effects of GA in combination with cisplatin.
Main Methods:
- Cytotoxicity was assessed using AlamarBlue and CCK08 assays.
- Apoptosis was evaluated via Hoechst staining and caspase-3 gene expression analysis (qRT-PCR).
- Cells tested included cisplatin-sensitive (A2780S), resistant (A2780CP) ovarian cancer cells, and normal ovarian (HOSE6-3) cells.
Main Results:
- Gallic acid monohydrate (GA) demonstrated dose-dependent cytotoxicity against all tested ovarian cancer cell lines.
- GA exhibited greater cytotoxicity than its congeners, with IC50 values of 19.39µg/mL (A2780S), 35.59 µg/mL (A2780CP), and 49.32µg/mL (HOSE6-3).
- Combination therapy of GA and cisplatin significantly enhanced cytotoxicity, particularly in chemoresistant A2780CP cells (p<0.05).
Conclusions:
- Gallic acid monohydrate (GA) exhibits significant cytotoxic effects on ovarian cancer cells, including chemoresistant lines.
- GA holds promise as a therapeutic agent to overcome cisplatin resistance in ovarian cancer.
- Further research into the anti-cancer properties of GA, especially in resistant ovarian cancer, is warranted.
