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

Oncol Lett. 2016 Dec;12(6):5122-5128. doi: 10.3892/ol.2016.5347. Epub 2016 Nov 3.


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.

Keywords: Notch3/NF-κB; diosmetin; hepatocellular carcinoma; p53/Bcl-2.