Abstract
Purpose
Cervical cancer is the second most prevalent cancer in women worldwide. Survival of patients has been improved by cisplatin-based chemotherapy, but its effectiveness is limited due to its adverse effects on many tissues, especially nephrotoxicity. To optimize the efficacy of CDDP, we propose a combination therapy using natural products with minimal side effects. Vitamin C being a natural antioxidant is capable of selectively targeting cancer cells at pharmacological concentrations. Vitamin C synergistically enhances the activity of chemotherapeutic agents without increasing toxicity to normal cells. Therefore, we exploited co-therapy with cisplatin and vitamin C to kill cervical cancer cells.
Methods
We elucidated the role of CDDP and VC on cervical cancer cell line (SiHa) by using cell growth assays, DNA fragmentation analysis, comet assay, in vitro morphological assessment of apoptosis (AO/EB and DAPI staining), ROS analysis by DCFDA, flow cytometry, biochemical assays (GST, GSH, NO, catalase, TPA) and Western blotting.
Results
Our results clearly demonstrated that CDDP and VC treatment exhibited ameliorative effect on induction of cell death by p53 overexpression and generation of hydrogen peroxide in SiHa cells, thereby reducing the dosage of CDDP required to induce cell death in cancer cells.
Conclusions
These studies provide novel approaches to combat cisplatin resistance in cervical cancer.
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Abbreviations
- CDDP:
-
Cisplatin
- VC:
-
Vitamin C
- GST:
-
Glutathione S-transferase
- GSH:
-
Reduced glutathione
- TPA:
-
Total peroxidase assay
- GPx:
-
Glutathione peroxidase
- ROS:
-
Reactive oxygen species
- AO:
-
Acridine orange
- EB:
-
Ethidium bromide
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Acknowledgments
Ankita Leekha is thankful to Jamia Millia Islamia for providing her Non-Net fellowship.
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Leekha, A., Gurjar, B.S., Tyagi, A. et al. Vitamin C in synergism with cisplatin induces cell death in cervical cancer cells through altered redox cycling and p53 upregulation. J Cancer Res Clin Oncol 142, 2503–2514 (2016). https://doi.org/10.1007/s00432-016-2235-z
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DOI: https://doi.org/10.1007/s00432-016-2235-z