Cancer Management and Research (Feb 2020)
Effects of Nicotinamide on Cervical Cancer-Derived Fibroblasts: Evidence for Therapeutic Potential
Abstract
Reem N Hassan,* Hualei Luo,* Weiying Jiang Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiying JiangDepartment of Medical Genetics, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74, Zhongshan Second Road, Yuexiu District, Guangzhou, Guangdong 510080, People’s Republic of ChinaTel +86-20-87331928Email [email protected]: The present study aimed to examine the effects of nicotinamide (NAM) on cervical cancer-associated fibroblasts (CAF) for its in vitro efficacy, gross inhibition, and mechanism of inhibition.Methods: The fibroblasts were treated with pre-specified concentrations of NAM followed by measurement of the cell proliferation using CCK-8 assay. The production of reactive oxygen species (ROS) was measured by 2ʹ,7ʹ-Dichlorofluorescin diacetate. We further investigated the apoptosis by flow cytometry using Annexin-V. We employed JC-1 assay to detect changes in the potential of the mitochondrial membrane. We further determined the expression of apoptotic genes was measured using qRT-PCR. And lastly, cell cycle experiments were conducted to determine the influence of NAM on arresting the growth of CAF in a cell cycle.Results: Our study showed that NAM was able to reduce fibroblasts viability. We specifically observed a significantly increased intracellular ROS with resultant exhaustion of cellular antioxidant defense machinery, including reduced glutathione (GSH). We further observed the involvement of mitochondrial pathway in the NAM induced apoptosis of fibroblasts.Conclusion: Our study supports the therapeutic potential of NAM for the treatment of cervical cancer and necessitates a further investigation of the reported findings.Keywords: apoptosis, cervical cancer, fibroblasts, mitochondrial pathway, nicotinamide, therapeutic potential
