Antrodia cinnamomea boosts the anti-tumor activity of sorafenib in xenograft models of human hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) has been recognized worldwide as one of the major causes of cancer death. The medicinal fungus Antrodia cinnamomea (A. cinnamomea) has been served as a functional food for liver protection. The aim of the present study was to investigate the potential activity of A. cinnamomea extracts as a safe booster for the anticancer activity of sorafenib, a multi-kinase inhibitor approved for the treatment of HCC. The biologically active triterpenoids in the ethanolic extracts of A. cinnamomea (EAC) were initially identified by HPLC/LC/MS then the different extracts and sorafenib were assessed in vitro and in vivo. EAC could effectively sensitize HCC cells to low doses of sorafenib, which was perceived via the ability of the combination to repress cell viability and to induce cell cycle arrest and apoptosis in HCC cells. The ability of EAC to enhance sorafenib activity was mediated through targeting mitogen-activated protein (MAP) kinases, modulating cyclin proteins expression and inhibiting cancer cell invasion. Moreover, the proposed combination significantly suppressed ectopic tumor growth in mice with high safety margins compared to single-agent treatment. Thus, this study highlights the advantage of combining EAC with sorafenib as a potential adjuvant therapeutic strategy against HCC.

Effect of ethanol extracts of Antrodia cinnamomea on head and neck squamous cell carcinoma cell line

“…Antcin-H, a type of triterpene isolated from Antrodia cinnamomea, was reported to inhibit proliferation and migration of human renal carcinoma 786-O cells by targeting MMPs and TIMPs (10). Furthermore, recent articles (12,13,16) revealed that EEA enhances chemosensitivity of several carcinomas, indicating that EEA can be used as adjuvant treatment combined with conventional chemotherapy. Several investigations have already shown the synergistic effects of EEA combined with cisplatin (16), sorafenib (12), and tamoxifen (13).…”

“…Furthermore, recent articles (12,13,16) revealed that EEA enhances chemosensitivity of several carcinomas, indicating that EEA can be used as adjuvant treatment combined with conventional chemotherapy. Several investigations have already shown the synergistic effects of EEA combined with cisplatin (16), sorafenib (12), and tamoxifen (13). The antitumor effect of EEA has been confirmed in a randomized controlled study, although the synergistic effects of EEA combined with chemotherapy were not observed (26).…”

“…Previous studies have established its anti-tumor effects (1,8,9). The protective role of the ethanol extract of fruiting bodies of Antrodia cinnamomea has been experimentally demonstrated in several malignancies including renal cancer (10), lung cancer (7,11), hepatocellular carcinoma (12), and breast cancer (13), while the effects on head and neck cancer were seldom evaluated (14). Several active components isolated from raw extracts of Antrodia cinnamomea, mainly including triterpenoids, dicarboxylic acids, and polysaccharides (15), have been identified and can effectively inhibit proliferation, invasion, and migration of tumor cells (10,14).…”

“…Several active components isolated from raw extracts of Antrodia cinnamomea, mainly including triterpenoids, dicarboxylic acids, and polysaccharides (15), have been identified and can effectively inhibit proliferation, invasion, and migration of tumor cells (10,14). Moreover, extracts of Antrodia cinnamomea were reported to sensitize lung cancer cells and hepatic carcinoma cells to chemotherapeutics (9,12,13,16,17), indicating it can serve as a promising source of adjuvant agents combined with conventional therapy. However the potential application of Antrodia cinnamomea in treatment of HNSCC remains unclear.…”

Antrodia cinnamomea —An updated minireview of its bioactive components and biological activity

“…In vivo study demonstrated that Sorafenib plus EAC greatly decreased tumor growth in nude mice than sorafenib or EAC treatment alone. All this suggest that combined treatment of EAC and sorafenib suppressed HCC tumor growth and could be a possible adjuvant curative approach to treat Hepatocellular carcinoma (HCC) (Wu et al, ).…”