Abstract
Antrodia cinnamomea (AC) is a medicinal fungal species that has been widely used traditionally in Taiwan for the treatment of diverse health-related conditions including cancer. It possesses potent anti-inflammatory and antioxidant properties in addition to its ability to promote cancer cell death in several human tumors. Our aim was to improve the anticancer activity of AC in hepatocellular carcinoma (HCC) through its cocultivation with ginger aiming at tuning the active ingredients. HCC cell lines, Huh-7 and HepG2 were used to study the in vitro anticancer activity of the ethanolic extracts of AC (EAC) alone or after the cocultivation in presence of ginger (EACG). The results indicated that the cocultivation of AC with ginger significantly induced the production of important triterpenoids and EACG was significantly more potent than EAC in targeting HCC cell lines. EACG effectively inhibited cancer cells growth via the induction of cell cycle arrest at G2/M phase and induction of apoptosis in Huh-7 and HepG2 cells as indicated by MTT assay, cell cycle analysis, Annexin V assay, and the activation of caspase-3. In addition, EACG modulated cyclin proteins expression and mitogen-activated protein kinase (MAPK) signaling pathways in favor of the inhibition of cancer cell survival. Taken together, the current study highlights an evidence that EACG is superior to EAC in targeting cancer cell survival and inducing apoptotic cell death in HCC. These findings support that EACG formula can serve as a potential candidate for HCC adjuvant therapy.
Highlights
Hepatocellular carcinoma is a common tumor influencing more than one million individuals worldwide every year (Mittal and El-Serag, 2013)
Various compounds have been identified in extracts of Antrodia cinnamomea (EAC), ethanolic extracts of AC cocultivated with ginger (EACG) and extracts of AC fruiting body (EACF) (Table 1 and Supplementary Material)
The results indicated that antcin B, dehydrosulphurenic acid, 3β,15α-dihydroxy-lanosta7,9(11),24-triene-21-oic acid and zhankuic acid C contents were significantly increased upon the cultivation of A. cinnamomea with ginger
Summary
Hepatocellular carcinoma is a common tumor influencing more than one million individuals worldwide every year (Mittal and El-Serag, 2013). HCC is the fifth most frequent cancer worldwide and the second most common cause of cancer death in the world (Omar et al, 2016b; Zhu et al, 2016). Many biological activities of AC have been demonstrated such as anti-inflammatory, cytotoxic and hepatoprotective properties. For anti-inflammatory activity, many compounds from AC have been reported. Considering the cytotoxic activity, it was reported that camphorataimide B displayed a potent anticancer activity in human breast cancer, leukemia cells, and human lung cancer cells (Lin et al, 2012). Some of the A. cinnamomea extract components such as methyl antcinate A, antcin B, and antcin K were able to induce apoptotic cell death in HCC (Hsieh et al, 2010, 2011; Huang et al, 2015; Lai et al, 2016)
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