Abstract
Although sorafenib, an oral multikinase inhibitor, was approved as a treatment drug of advance hepatocellular carcinoma (HCC), treatment efficacy still requires improvement. Searching for the adjuvant reagent for enhancing sorafenib efficacy remains as a critical issue. Sorafenib has been proved to suppress extracellular signal-regulated kinases (ERK) in HCC; however, protein kinase B (AKT) was not affected by it. Targeting AKT in combination with sorafenib could be an important breakthrough point of HCC treatment. Many herbal compounds and composite formulas have been shown to enhance anti-HCC activity of sorafenib. Magnolol is a bioactive compound extracted from the bark of the Magnolia officinalis and has been shown to induce apoptosis and inhibit cell invasion in HCC in vitro. However, whether magnolol sensitizes HCC to sorafenib is ambiguous. In this study, we indicated that magnolol significantly enhanced sorafenib-diminished tumor cell growth, expression of anti-apoptotic proteins, and migration/invasion ability compared to sorafenib alone. Magnolol significantly boosted sorafenib-induced extrinsic/intrinsic dependent apoptosis pathways in HCC. Notably sorafenib could not reduce protein level of AKT (Ser473), but expression of AKT (Ser473) was significantly decreased by magnolol or magnolol combined with sorafenib. LY294002 as specific AKT inhibitor was used to confirm that AKT inactivation may promote anticancer effect of sorafenib. Taken together, AKT inhibition is associated with magnolol-enhanced the therapeutic effect of sorafenib in HCC. We suggested magnolol as the potential adjuvant which may enhance therapeutic benefits of sorafenib in patients with HCC.
Highlights
Herbal medicines, natural products from medicinal plants, can reduce inflammatory response and be used to treat liver disease [1]
A flavonoid extracted from Curcuma longa, has been indicated to induce apoptosis, cell cycle arrest, and reduce angiogenic and metastatic activity leading to the inhibition of tumor progression in hepatocellular carcinoma (HCC) in vitro and in vivo [6,7,8]
We evaluated whether sorafenib may markedly reduce cell viability via combination with magnolol as compared with mono-treatment
Summary
Natural products from medicinal plants, can reduce inflammatory response and be used to treat liver disease [1]. Many herbal compounds and composite formula are chemopreventive agents that prevent liver carcinogenesis in patients with cirrhosis. Both glycyrrhizin (aqueous extract of the liquorice root) and sho saiko-to (TJ-9) have been found to be effective in inhibiting development of hepatocellular carcinoma (HCC) [2,3]. Herbal compounds and composite formula inhibit tumor growth through induction of apoptosis, cell cycle arrest and blockage of intracellular signal transduction in HCC [5]. A flavonoid extracted from Curcuma longa, has been indicated to induce apoptosis, cell cycle arrest, and reduce angiogenic and metastatic activity leading to the inhibition of tumor progression in HCC in vitro and in vivo [6,7,8]. Lin et al presented shenqi mixture (SQM), an herbal composite formula, enhances anti-HCC efficacy of microwave coagulation therapy and improves survival rate and patients’
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
