Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice
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Tse-Hung Huang1,2, Yi-Han Chiu3, Yi-Lin Chan4, Hang Wang3,5, Tsung-Lin Li6, Chien-Yin Liu7, Cheng-Ta Yang7,8, Tzung-Yan Lee2,9,10, Jyh-Sheng You2,9,10, Kuang-Hung Hsu2,11, Chang-Jer Wu3,12
1Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan
2Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Taoyuan, Taiwan
3Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan
4Department of Life Science, Chinese Culture University, Taipei, Taiwan
5Institute of Biomedical Nutrition, Hung Kuang University, Taichung, Taiwan
6Genomics Research Center, Academia Sinica, Taipei, Taiwan
7Department of Thoracic Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
8Department of Respiratory Care, Chang Gung University, Taoyuan, Taiwan
9Graduate Institute of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
10School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan
11Laboratory for Epidemiology, Department and graduate institute of health care management, Chang Gung University, Taoyuan, Taiwan
12Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan
Chang-Jer Wu, e-mail: [email protected]
Kuang-Hung Hsu, e-mail: [email protected]
Keywords: antrodia cinnamomea, cisplatin, hepatotoxicity, lung cancer
Received: March 25, 2015 Accepted: June 17, 2015 Published: June 27, 2015
Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death.
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