Antrodia cinnamomea Extract Attenuates Cisplatin-Induced Muscle Atrophy, Apoptosis, and Cell Growth Suppression

Antrodia cinnamomea (AC), a potential medicinal fungus which possesses anti-inflammatory and anticancer activities, has been previously reported to be able to ameliorate muscle wasting in cisplatin-treated lung tumor-bearing mice via AC extract. However, whether AC extract modulates muscle cell differentiation, apoptosis, and cell cycle progression remains unclear. Here, we show that the ethanol extract of AC (EEAC) significantly restored cisplatin-reduced quadricep mass in mice. EEAC attenuated cisplatin/gemcitabine (C/G)-suppressed elongated myotube formation, which is differentiated from C2C12 cells. Moreover, EEAC synergized with C/G to inhibit cell growth of LLC1 cells, whereas EEAC attenuated C/G-reduced proliferation of C2C12 cells. Although EEAC protected C/G-induced apoptosis of both LLC1 and C2C12, EEAC suppressed cyclin D expression in LLC1 while partially restoring C/G-reduced cyclin D level in C2C12 cells. Finally, as $\mathrm{p}53$ and $\mathrm{p}21$ participate in inducing skeletal muscle atrophy, we found that C/G induced $\mathrm{p}53$ and $\mathrm{p}21$ expression in C2C12 cells but with its effect significantly attenuated by EEAC. Our findings indicate that AC extract is a potential natural agent for attenuating cisplatin-induced muscle atrophy. Practical Applications. Muscle atrophy is one of the major side effects caused by chemotherapy. In addition to inducing cell death, chemotherapeutic agents inhibit cell growth of both cancer and normal cells as well. Our current findings indicated that AC extract attenuates cisplatin-induced muscle wasting and apoptosis of C2C12 cells. AC extract is a potential dietary supplement used for ameliorating chemotherapy-induced muscle atrophy.