ZINC OXIDE NANORODS INDUCED APOPTOSIS IN HUMAN PROSTATIC AND HEPATOCELLULAR CARCINOMA VIA MITOCHONDRIA DYSFUNCTION MEDIATED THOUGH BAX/ BCL-2 WITH P53 ACTIVATION

Abstract

The present study aimed to experimentally synthesis zinc oxide nanorods (ZnO NRs) using albumin as bio-template by a sol-gel method and to characterize the products using UV-Visible, FTIR, XRD, TGA and HRTEM. The crystallinity and morphology of the ZnO NRs were confirmed to have an average diameter of 70 nm and 250 nm length. The formation mechanism depends on the nucleation of Zn+2 in sites of the albumin followed by Zn+2 assembly in the cavity of albumin and finally thermal treatment to form ZnO in rod shape then calcination to final form ZnO NRs form as shown in HRTEM. Cytotoxicity of developed ZnO-NRs was conducted using MTT assay on both HepG2 and PC-3 cells. Data revealed that ZnO-NPs were toxic to both HepG2 and PC-3 cell lines displayed a concentration dependent viability. The flow cytometry illustrated that apoptosis of hepatocellular carcinoma (HepG2) depends on the cell growth arrest at G1/S phase indicated that inhibition Cyclin E (CDK 2) while prostatic carcinoma (PC-3) depends cell growth arrest at G2/M phase indicated that inhibition of Cyclin ACDK1. The apoptotic mechanism was investigated using rt-PCR. The apoptotic mechanism in both cell lines HepG2 and PC-3 was depended on the upregulated of Bax protein and down regulation of Bcl-2 indicated that the mechanism of mitochondrial outer membrane permeability (MOMP) or mitochondria dysfunction was dependent on activation of P53 protein.