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

Qiao,Jie; Liu,Jie; Jia,Kaiqiao; Li,Ning; Liu,Bin; Zhang,Qingyu; Zhu,Runzhi

doi:10.3892/ol.2016.5347

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

Authors:
- Jie Qiao
- Jie Liu
- Kaiqiao Jia
- Ning Li
- Bin Liu
- Qingyu Zhang
- Runzhi Zhu
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Affiliations: Laboratory of Hepatobiliary Surgery, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Laboratory of Hematology, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
Published online on: November 3, 2016 https://doi.org/10.3892/ol.2016.5347
Pages: 5122-5128
Copyright: © Qiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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