Vanadium complex induced apoptosis in HepG2 Cells by the up-regulation of p53, p21, and Caspase-8

OBJECTIVE: The anti-cancer effects of 4-bromo-2-(((5-chloro-2-hydroxyphenyl) imino) methyl) phenol ([IV(L)] complex) have been verified. The main mechanisms used by the [IV(L)] complex to induce apoptosis in cancer cells have yet to be clarified. This study has been designed to explore the effects of the [IV(L)] complex on the expression of apoptosis-related genes, including P53, caspase-8, bax, bcl-2, bim, P21, and bid, in human liver hepatocellular carcinoma (HepG2) cell lines and mouse fibroblast cells (L929), as normal cells. MATERIALS AND METHODS: The RPMI medium was used to culture L929 and HepG2 cells at the IC50 concentration of the [IV(L)] complex. The expression of some apoptosis-related genes (p53, caspase-8, bax, bcl-2, bim, P21, and bid) was evaluated before and after 48 h from treating the cells by the [IV(L)] complex at the IC50 concentration using the real-time PCR. Data analyzed via SPSS 18 (SPSS Inc., Chicago, IL, USA) software and p< 0.05 was designated as the significant level. RESULTS: The [IV(L)] complex increased the mRNA expression levels of P53 and P21 genes in HepG2 (p< 0.05) cells. In addition, the expression levels of caspase-8 and bid decreased after treatment with the [IV(L)] complex (p= 0.05), and the expression levels of bax and bim genes remained fixed in the HepG2-treated cells. In L929 cells, the mRNA expression levels of P53, caspase-8, bim, P21, and bid increased, with the expression level of the bax gene significantly decreased after 48 h from treatment with the [IV(L)] complex(p= 0.001). CONCLUSIONS: The Vanadium [IV(L)] complex induced apoptosis in HepG2 cells using the P53-P21 pathway-dependent method. In L929 cells, the mRNA expression levels of caspase-8 and bid were up-regulated in the treated cells. Therefore, it seems that apoptosis is triggered by both the P53-P21 pathway and the extrinsic apoptotic pathway in L929 cells.