Enhancing the Anticancer Activity of Antrodia cinnamomea in Hepatocellular Carcinoma Cells via Cocultivation With Ginger: The Impact on Cancer Cell Survival Pathways

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.

Effect of ginger (Zingiber officinale) on semen quality

“…Generally, ginger roots (rhizomes) are widely used as a food spice (Eliopoulos, ). In addition, it is commonly used in traditional medicine because of its inherited and evidence‐based health benefits in wide‐range of diseased conditions/disorders such as cancers (Chen et al, ; Saha et al, ; Salafzoon, Mahmoodzadeh Hosseini, & Halabian, ), diabetes (Al Hroob, Abukhalil, Alghonmeen, & Mahmoud, ; Zhu, Chen, Song, Wang, & Sun, ), cardiovascular disease (Liu et al, ; Nicoll & Henein, ), male infertility (Banihani, ; Hosseini et al, ), ulcer (Liu et al, ; Wang et al, ), depression (Kukula‐Koch et al, ), rheumatoid arthritis (Funk, Frye, Oyarzo, & Timmermann, ), Alzheimer (Cuya, Baptista, Franca, & T., ) and nonalcoholic fatty liver disease (Sahebkar, ). In actual fact, the impact of ginger on human health is attributable to its potent bioactive properties such as antioxidant (Danwilai, Konmun, Sripanidkulchai, & Subongkot, ; Masuda, Kikuzaki, Hisamoto, & Nakatani, ), anti‐inflammatory (Jeena, Liju, & Kuttan, ), immuno‐modulatory (Ali, Blunden, Tanira, & Nemmar, ), antimicrobial (Park, Bae, & Lee, ) and anti‐tumorigenic properties (Ali et al, ).…”

Ginger and Testosterone

“…Ginger ( Zingiber officinale ) is a flowering medicinal plant whose root, or rhizome (plant stem) is commonly used as a spice [1]. Additionally, it is widely used in folk medicine because of its many health benefits in various diseases, including chronic diseases such as diabetes [2,3], cancer [4,5,6], ulcer [7,8], Alzheimer [9], cardiovascular disease [10,11], and depression [12]. The beneficial effect of ginger in such diseases is mainly due to its antioxidant [13,14], antimicrobial [15], and anti-inflammatory properties [16].…”

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

“…EACG‐induced apoptosis Huh‐7 and HepG2 cells by decreasing cell viability and by increasing G2/M phase accumulation and caspase‐3 clevage. Evidence from this study showed that EACG formula can be better used in treating HCC patients (Chen et al, ).…”

“…A . cinnamomea has hepatoprotective property, therefore Chen et al, used ethanolic extracts of A. cinnamomea (EAC) to enhance sorafenib anticancer activity in hepatoceullular carcinoma (Chen et al, ). Sorafenib with EAC inhibited HepG2 and Huh‐7 cell viability and induced apoptosis by Caspase‐3 cleavage.…”

“…Antrodia cinnamomea (AC), an edible Taiwanese mushroom is considered as important natural resources due to its medicinal and biological properties (Chen et al, ; Huang, Wang, Nguyen, & Kuo, ). It is considered as a precious medicinal mushroom in Taiwan, also known as “Niu‐Chang‐Chih” in Chinese.…”