Nicotinamide induces mitochondrial-mediated apoptosis through oxidative stress in human cervical cancer HeLa cells

• Published in: Life sciences (1973) Vol. 181; pp. 62 - 69
• Main Authors: Feng, Yi, Wang, Yonghua, Jiang, Chengrui, Fang, Zishui, Zhang, Zhiqiang, Lin, Xiaoying, Sun, Liwei, Jiang, Weiying
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.07.2017; Elsevier BV
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cancer; Cancer therapies; Cell proliferation; Cell Proliferation - drug effects; Cervical cancer; Cervix; Chemical compounds; Chemotherapy; Cholecystokinin; Cytometry; Drugs; Energy metabolism; Female; Flow Cytometry; Fluorescence; Gene expression; HeLa Cells; Humans; Immunoblotting; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Metabolism; Microscopy, Fluorescence; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial apoptotic pathway; Niacinamide - administration & dosage; Niacinamide - pharmacology; Nicotinamide; Oxidation-Reduction - drug effects; Oxidative stress; Oxidative Stress - drug effects; Pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Studies; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - pathology; Oxidative stress; Nicotinamide; Mitochondrial apoptotic pathway; Cervical cancer
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2017.06.003

Nicotinamide participates in energy metabolism and influences cellular redox status and modulates multiple pathways related with both cellular survival and death. Recent studies have shown that it induced proliferation inhibition and apoptosis in many cancer cells. However, little is known about the effects of nicotinamide on human cervical cancer cells. We aimed to evaluate the effects of the indicated concentrations nicotinamide on cell proliferation, apoptosis and redox-related parameters in HeLa cells and investigated the apoptotic mechanism. After the treatment of the indicated concentrations nicotinamide, HeLa cell proliferation was evaluated by the CCK-8 assay and the production of ROS (reactive oxygen species) was measured using 2′,7′-Dichlorofluorescin diacetate. The apoptotic effect was confirmed by observing the cellular and nuclear morphologies with fluorescence microscope and apoptotic rate of HeLa cell apoptosis was measured by flow cytometry using Annexin-V method. Moreover, we examined the mitochondrial membrane potential by JC-1 method and measured the expression of apoptosis related genes using qRT-PCR and immunoblotting. Nicotinamide restrained the HeLa cell proliferation and significantly increased the accumulation of ROS and depletion of GSH at relatively high concentrations. Furthermore, nicotinamide promoted HeLa cell apoptosis via the intrinsic mitochondrial apoptotic pathway. Our study revealed that nicotinamide induced the apoptosis through oxidative stress and intrinsic mitochondrial apoptotic pathways in HeLa cell. The results emerge that nicotinamide may be an inexpensive, safe and promising therapeutic agent or a neoadjuvant chemotherapy for cervical cancer patients, as well useful to find new drugs for cervical cancer therapy.