Diosmetin Induces Cell Apoptosis by Regulating CYP1A1/CYP1A2 Due to p53 Activation in HepG2 Cells.

It was explored that CYP1 family of cytochromes P450 were over-expressed in several types of cancer. Our study aimed to characterize anti-proliferative activity and metabolism of the natural flavonoid diosmetin in the human hepatoma cell HepG2, expressing CYP1 family. Diosinduced cell apoptosis could be reversed due to p53 blockade and the cellular P53 and CYP1A1/CYP1A2 proteins levels were examined. P53 and CYP1A1/CYP1A2 proteins were upregulated by Dios; when PFT-α was added into cells, the P53 levels were down-regulated accompanied with up-regulated CYP1A1/CYP1A2. Meanwhile, when cells were co-treated with Dios and PFT-α, P53 was down-regulated and CYP1A1/CYP1A2 up-regulated controlled with that of Dios treated cells. The data reveal the new evidence that cytochrome P450 CYP1A regulation by P53 enzyme plays an important role in Diosmetin anti-cancer activity of HepG2 cells.

Diosmetin triggers cell apoptosis by activation of the p53/Bcl-2 pathway and inactivation of the Notch3/NF-κB pathway in HepG2 cells.

Diosmetin (DIOS), a flavonoid compound, is abundant in Citrus limon. Emerging studies have shown that DIOS is an effective compound implicated in multiple types of cancer. However, whether DIOS serves a role in hepatocellular carcinoma (HCC) is still obscure. HepG2 cells were used in the present study, and it was observed that DIOS exhibited antitumor activity against liver cancer cells. Western blotting was performed to evaluate cell apoptosis and survival-associated proteins, and the results demonstrated that DIOS treatment resulted in the activation of the p53-dependent apoptosis pathway. Our results revealed that DIOS caused inhibition of the nuclear factor (NF)-κB signaling pathway and downregulation of Notch3 receptor. Furthermore, by using small hairpin RNA-Notch3, it was confirmed that DIOS inhibited the NF-κB signaling pathway by inactivation of Notch3. In conclusion, the present results demonstrated that DIOS triggered cell apoptosis by activation of the p53 signaling pathway and inhibited the NF-κB cell survival pathway by downregulation of Notch3 receptor expression. DIOS is a potential agent for prevention of HCC.