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Progress in the Use of Molecular Hydrogen for Cancer Treatment

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Journal of Nutritional Oncology, August 15, 2019, Volume 4, Number 3 · 103 · Progress in the Use of Molecular Hydrogen for Cancer Treatment Dong Yue Du, Yun Hua Peng, Jian Kang Liu, Jian Gang Long Center for Mitochondrial Biology and Medicine, Biomedical Information Engineering Laboratory of State Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China Abstract: Molecular hydrogen is an effective antioxidant. Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases. The possibility of using hydrogen in the treatment of cancer was first discovered in 1975, and in recent studies, researchers have reported numerous positive effects of hydrogen in cancer therapy, including: 1) the alleviation of complications caused by chemotherapy; 2) a reduction of complications caused by radiotherapy; 3) delays in the progression of cancer; and 4) enhanced efficacy of conventional therapy when used in combination with hydrogen. This article reviews the research progress in the use of hydrogen in the treatment of cancer, and proposes future directions for research in this field. Key words: Molecular hydrogen; Cancer; Chemotherapy; Radiotherapy; Anticancer drug; Complications; Quality of life Introduction Hydrogen is the smallest molecule, and is a colorless, tasteless, odorless, and nontoxic gas at ambient tempera- tures [1]. Over the past few decades, there has been ex- tensive researches on the beneficial effects of hydrogen in the clinical setting, including studies of its anti-oxidative, anti-inflammatory and potential anti-cancer activity [2]. The possibility of using hydrogen in the treatment of cancer was first described by Dore M et al. in 1975. They reported that hyperbaric hydrogen treatment for 2 weeks could lead to significant regression of skin carcinomas in mice [3]. However, concerns about the safety of trans- porting, storing and administering hyperbaric hydrogen limited the application of this therapy. However, in 2007, Ohsawa I et al. suggested that inhaling small amounts of hydrogen gas could selectively reduce the level of oxygen radicals, and could protect neurons from injury caused by ischemia-reperfusion or inflammation [4]. Since then, the potential therapeutic effects of molecular hydrogen have at- tracted increasing attention. Several studies have shown that hydrogen has positive effects against metabolic syndrome, inflammation, injury, and cancer [5]. The application of hydrogen for cancer treatment is now a hot research topic. Clinical and experimental research has indicated that hydrogen could reduce complications associated with treatment using conventional anti-cancer drugs, could prevent cancer progression and could improve the quality of life of cancer patients. In this article, we re- view the progress made in the application of hydrogen for the prevention and treatment of cancer, and propose future Corresponding author: Jian Gang Long, PhD, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, Xi’an Jiaotong University, 28 West Xianning Road, Xi’an 710049, China; Tel: +86 199 2907 2355; Email: jglong@mail.xjtu.edu.cn directions for research on the potential use of molecular hy- drogen for cancer therapy. Hydrogen Reduces the Complications Associ- ated with Chemotherapy Chemotherapy is commonly used for most types of cancer, as has been the mainstay of treatment for decades. However, these antitumor drugs are often cytotoxic, and also cause damage to normal cells and organs [6], poten- tially leading to complications such as nephrotoxicity, car- diotoxicity and hepatotoxicity. These side effects strongly decrease the life quality of cancer patients. Studies have found that human tumor cells produce more reactive oxygen species (ROS) than normal cells, thus promoting the proliferation, angiogenesis, and DNA synthe- sis of cancer cells [7]. Nakashima-Kamimura N et al. found that inhaling hydrogen or drinking hydrogen-rich water, which is water contains a high concentration of dissolved hydrogen, could alleviate the nephrotoxicity caused by cisplatin, an anti-cancer drug, without affecting the drug’s anti-tumor activity [8]. Doxorubicin (DOX) is widely used as an anticancer drug, but its cardiotoxicity and hepatotoxicity limit its application [9]. It was reported that hydrogen-rich saline treatment could effectively inhibit the heart and liver injury, as well as the inflammation caused by DOX [9]. Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which is an effective drug used in the treatment of non-small cell lung cancer. However, it can cause acute lung injury [10]. Terasaki Y et al. recently reported that hydro- gen water intake could effectively protect the lungs of mice from severe damage caused by gefitinib without interfering with the anti-tumor activity of the drug [10]. Hydrogen wa- ter also alleviated the liver injury caused by mFOLFOX6 chemotherapy in colorectal cancer patients [6].

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