title: Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest.
abstract: A natural predominant flavanone naringenin, especially abundant in citrus fruits, has a wide range of pharmacological activities. The search for antiproliferative agents that reduce skin carcinoma is a task of great importance. The objective of this study was to analyze the anti-proliferative and apoptotic mechanism of naringenin using MTT assay, DNA fragmentation, nuclear condensation, change in mitochondrial membrane potential, cell cycle kinetics and caspase-3 as biomarkers and to investigate the ability to induce reactive oxygen species (ROS) initiating apoptotic cascade in human epidermoid carcinoma A431 cells. Results showed that naringenin exposure significantly reduced the cell viability of A431 cells (p<0.01) with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed statistically significant (p<0.001) dose-related increment in ROS production for naringenin. It also caused naringenin-mediated epidermoid carcinoma apoptosis by inducing mitochondrial depolarization. Cell cycle study showed that naringenin induced cell cycle arrest in G0/G1 phase of cell cycle and caspase-3 analysis revealed a dose dependent increment in caspase-3 activity which led to cell apoptosis. This study confirms the efficacy of naringenin that lead to cell death in epidermoid carcinoma cells via inducing ROS generation, mitochondrial depolarization, nuclear condensation, DNA fragmentation, cell cycle arrest in G0/G1 phase and caspase-3 activation.
authors.affiliation: Department of Zoology, Shibli National (PG) College, Azamgarh, Uttar Pradesh, India.
authors.forename: Md Sultan
authors.initials: MS
authors.lastname: Ahamad
authors.affiliation: Molecular Endocrinology Lab, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India.
authors.forename: Sahabjada
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: Department of Zoology, Shibli National (PG) College, Azamgarh, Uttar Pradesh, India.
authors.forename: Asif
authors.initials: A
authors.lastname: Jafri
authors.affiliation: Department of Zoology, D S College, Aligarh, Uttar Pradesh, India.
authors.forename: Sheeba
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Human Genetics and Toxicology Laboratory, Department of Zoology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Afzal
authors.affiliation: Molecular Endocrinology Lab, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India.
authors.forename: Md
authors.initials: M
authors.lastname: Arshad
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D053148:Caspase 3 / Q000096:biosynthesis; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D017382:Reactive Oxygen Species; D053148:Caspase 3; C005273:naringenin