Title:Targeting the HIF-1α/Cav-1 Pathway with a Chicory Extract/Daidzein Combination Plays a Potential Role in Retarding Hepatocellular Carcinoma
Volume: 21
Issue: 10
Author(s): Sherin Zakaria, Reem Nawaya, Nabil M. Abdel-Hamid, Ramadan A. Eldomany and Mamdouh M. El-Shishtawy*
Affiliation:
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516,Egypt
Keywords:
Hepatocellular carcinoma, diethyl nitrosamine, chicory leaf extract, daidzein, hypoxia-inducible factor-1α, caveolin-
1.
Abstract:
Background: Hepatocellular carcinoma (HCC) is one of the most rapidly growing solid
cancers, that is characterized by hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is a transcription
factor that regulates tumor proliferation and metastasis. It induces caveolin-1 (Cav-1) expression, a
glycoprotein found on the membrane surface, then Cav-1 triggers angiogenesis and metastasis in
HCC.
Objective: We hypothesize that targeting HIF-1α and consequently, Cav-1 using the antioxidant natural
compound such as chicoric acid and a Cav-1 inhibitor daidzein (DAZ) could be a useful approach
in the management of HCC. This study was conducted to investigate the possible therapeutic
efficacy of standardized chicory leaf extract (SCLE) and DAZ via modulation of HIF-1α and
Cav-1 in HCC rats.
Methods: Diethyl nitrosamine (DENA) was used for HCC induction. After the induction period,
four groups (10 rats for each) were treated with SCLE, DAZ, a combination of both, as well as sorafenib,
all compared to the non-treated control. We assessed hepatic HIF-1α protein expression,
Cav-1 gene expression, serum level of AFP, hepatic tissue content of VEGF, MMP-9, oxidative
stress markers MDA and SOD.
Results: DAZ, SCLE, and their combination, significantly down-regulated the expression of
HIF-1α, Cav-1, and consequently dampened MMP-9, VEGF, hepatic content. It has been observed
that the combination treatment showed a synergistic effect compared to either treatment alone. Importantly,
the combination treatment exhibited a significantly more potent effect than sorafenib.
Conclusion: This study showed the potential role of the HIF-1α/Cav-1 pathway in HCC progression,
moreover, SCLE and DAZ showed a potent efficacy in retarding HCC via modulation of this
pathway.
