Ankita Leekha1,2, Bahadur S Gurjar1, Aakriti Tyagi1, Moshahid A Rizvi2, Anita K Verma3. 1. NanoBiotech Laboratory, Department of Zoology, Kirori Mal College, University of Delhi , Delhi, 110007, India. 2. Genome Biology Laboratory, Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India. 3. NanoBiotech Laboratory, Department of Zoology, Kirori Mal College, University of Delhi , Delhi, 110007, India. akamra23@hotmail.com.
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.
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.
Authors: J Céraline; G Deplanque; B Duclos; J M Limacher; A Hajri; F Noel; C Orvain; T Frébourg; C Klein-Soyer; J P Bergerat Journal: Int J Cancer Date: 1998-01-30 Impact factor: 7.396
Authors: Ali Mussa; Ros Akmal Mohd Idris; Naveed Ahmed; Suhana Ahmad; Ahmad Hafiz Murtadha; Tengku Ahmad Damitri Al Astani Tengku Din; Chan Yean Yean; Wan Faiziah Wan Abdul Rahman; Norhafiza Mat Lazim; Vuk Uskoković; Khalid Hajissa; Noor Fatmawati Mokhtar; Rohimah Mohamud; Rosline Hassan Journal: Pharmaceuticals (Basel) Date: 2022-06-03