Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice.

// Tse-Hung Huang 1, 2 , Yi-Han Chiu 3 , Yi-Lin Chan 4 , Hang Wang 3, 5 , Tsung-Lin Li 6 , Chien-Yin Liu 7 , Cheng-Ta Yang 7, 8 , Tzung-Yan Lee 2, 9, 10 , Jyh-Sheng You 2, 9, 10 , Kuang-Hung Hsu 2, 11 , Chang-Jer Wu 3, 12 1 Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan 2 Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Taoyuan, Taiwan 3 Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan 4 Department of Life Science, Chinese Culture University, Taipei, Taiwan 5 Institute of Biomedical Nutrition, Hung Kuang University, Taichung, Taiwan 6 Genomics Research Center, Academia Sinica, Taipei, Taiwan 7 Department of Thoracic Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan 8 Department of Respiratory Care, Chang Gung University, Taoyuan, Taiwan 9 Graduate Institute of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan 10 School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan 11 Laboratory for Epidemiology, Department and graduate institute of health care management, Chang Gung University, Taoyuan, Taiwan 12 Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan Correspondence to: Chang-Jer Wu, e-mail: wuchangjer@yahoo.com.tw Kuang-Hung Hsu, e-mail: khsu@mail.cgu.edu.tw Keywords: antrodia cinnamomea, cisplatin, hepatotoxicity, lung cancer Received: March 25, 2015      Accepted: June 17, 2015      Published: June 27, 2015 ABSTRACT 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.