title: Zinc enhances CDKN2A,pRb1 expression and regulates functional apoptosis via upregulation of p53 and p21 expression in human breast cancer MCF-7 cell.
abstract: Zinc (Zn) is an essential trace elements, its deficiency is associated with increased incidence of human breast cancer. We aimed to study the effect of Zn on human breast cancer MCF-7 cells cultured in Zn depleted and Zn adequate medium. We found increased cancer cell growth in zinc depleted condition, further Zn supplementation inhibits the viability of breast cancer MCF-7 cell cultured in Zn deficient condition and the IC25,IC50value for Zn is 6.2μM, 15μM, respectively after 48h. Zn markedly induced apoptosis through the characteristic apoptotic morphological changes and DNA fragmentation after 48h. In addition, Zn deficient cells significantly triggered intracellular ROS level and develop oxidative stress induced DNA damage; it was confirmed by elevated expression of CYP1A, GPX, GSK3β and TNF-α gene. Zinc depleted MCF-7 cells expressed significantly (p≤0.001) decreased levels of CDKN2A, pRb1, p53 and increased the level of mdm2 expression. Zn supplementation (IC50=15μM), increased significantly CDKN2A, pRB1 & p53 and markedly reduced mdm2 expression; also protein expression levels of CDKN2A and pRb1 was significantly increased. In addition, intrinsic apoptotic pathway related genes such as Bax, caspase-3, 8, 9 & p21 expression was enhanced and finally induced cell apoptosis. In conclusion, physiological level of zinc is important to prevent DNA damage and MCF-7 cell proliferation via regulation of tumor suppressor gene.
authors: Cancer Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors: Nada
authors: N
authors: Al-Saran
authors: Cancer Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia. Electronic address: subashbabu80@gmail.com.
authors: Pandurangan
authors: P
authors: Subash-Babu
authors: Cancer Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors: Doha M
authors: DM
authors: Al-Nouri
authors: Cancer Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors: Hanan A
authors: HA
authors: Alfawaz
authors: Cancer Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia. Electronic address: alshatwi@ksu.edu.sa.
authors: Ali A
authors: AA
authors: Alshatwi
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D003470:Culture Media; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D055273:Salivary Proline-Rich Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D015032:Zinc / Q000172:deficiency / Q000494:pharmacology*
chemical_list: C493956:CDKN1A protein, human; C000614131:CDKN2A protein, human; D003470:Culture Media; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; C524744:PRB1 protein, human; D017382:Reactive Oxygen Species; D055273:Salivary Proline-Rich Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D015032:Zinc
keywords: Apoptosis; Chelex; MCF-7 breast cancer cell; Proliferation; Zinc