Vitamin C in synergism with cisplatin induces cell death in cervical cancer cells through altered redox cycling and p53 upregulation.
OBJECTIVE
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.
NanoBiotech Laboratory, Department of Zoology, Kirori Mal College, University of Delhi , Delhi, 110007, India.|Genome Biology Laboratory, Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
Ankita
A
Leekha
NanoBiotech Laboratory, Department of Zoology, Kirori Mal College, University of Delhi , Delhi, 110007, India.
Bahadur S
BS
Gurjar
NanoBiotech Laboratory, Department of Zoology, Kirori Mal College, University of Delhi , Delhi, 110007, India.
Aakriti
A
Tyagi
Genome Biology Laboratory, Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
Moshahid A
MA
Rizvi
NanoBiotech Laboratory, Department of Zoology, Kirori Mal College, University of Delhi , Delhi, 110007, India. akamra23@hotmail.com.
Anita K
AK
Verma
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D001205:Ascorbic Acid; D002945:Cisplatin
Apoptosis; Cervical cancer; Cisplatin; Oxidative stress; Vitamin C; p53