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Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment
  1. Kazue Yamagishi1,
  2. Kazuo Onuma1,
  3. Yota Chiba1,
  4. Shinya Yagi2,
  5. Shigenobu Aoki3,
  6. Tomoyuki Sato4,
  7. Yasushi Sugawara5,
  8. Noriyasu Hosoya6,
  9. Yasutake Saeki7,
  10. Minoru Takahashi8,
  11. Masayoshi Fuji8,
  12. Takeo Ohsaka9,
  13. Takeyoshi Okajima9,
  14. Kenji Akita10,
  15. Takashi Suzuki11,
  16. Pisol Senawongse12,
  17. Akio Urushiyama13,
  18. Kiyoshi Kawai14,
  19. Hirofumi Shoun15,
  20. Yoshimasa Ishii16,
  21. Hiroya Ishikawa17,
  22. Shigeru Sugiyama18,
  23. Madoka Nakajima19,
  24. Masaru Tsuboi19,
  25. Tateo Yamanaka20
  1. 1FAP Dental Institute, Tokyo, Japan
  2. 2Department of Quantum Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Aichi, Japan
  3. 3Faculty of Social and Information Studies, Gunma University, Maebashi, Gunma, Japan
  4. 4Center of Colorectal Disease and Pelvic Floor Dysfunction, Saitama Shinkaibashi Clinic, Saitama city, Saitama, Japan
  5. 5Department of Plastic Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
  6. 6Department of Periodontics and Endodontics, Tsurumi University, School of Dental Medicine, Yokohama, Kanagawa, Japan
  7. 7Department of Physiology, Tsurumi University, School of Dental Medicine, Yokohama, Kanagawa, Japan
  8. 8Nagoya Institute of Technology, Tajimi, Gifu, Japan
  9. 9Department of Electrical Chemistry, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan
  10. 10Department of Respiratory Medicine, Nagoya Central Hospital, Nagoya, Aichi, Japan
  11. 11Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Yamanashi University, Kofu, Yamanashi, Japan
  12. 12Department of Operative Dentistry, Faculty of Dentistry, Mahidol University, Bangkok, Thailand
  13. 13Department of Chemistry, College of Science, St. Paul's (Rikkyo) University, Tokyo, Japan
  14. 14Department of Nutrition, Faculty of Wellness, Shigakkan University, Ohbu, Aichi, Japan
  15. 15Department of Biotechnology, Graduate School of Agricultural and Life Science, University of Tokyo, Tokyo, Japan
  16. 16Dentistry/Oral and Maxillofacial Surgery, Ebina General Hospital, 1320 Kawaraguchi, Ebina, Kanagawa, Japan
  17. 17Department of Nutrition and Health Science, Faculty of Human Environmental Science, Fukuoka Women's University, Fukuoka, Japan
  18. 18Graduate School of Engineering, Osaka University, Suita, Osaka, Japan
  19. 19Bio-Safty Research Center, Foods, Drugs, and Pesticides (BSRC), Iwata, Shizuoka, Japan
  20. 20Tokyo Institute of Technology, Kochi, Japan
  1. Correspondence to Dr Kazue Yamagishi, FAP Dental Institute, 3-2-1, Kakinokizaka, 502, Meguro-ku, Tokyo 152-0022, Japan; fzt02705{at}


Background and aims The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation.

Methods Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells.

Results Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect.

Conclusions Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.

  • Hydrogen sulfide
  • glucose metabolism
  • colorectal cancer
  • cancer
  • oncogenes
  • adhesion molecules
  • mutations
  • gene mutation
  • genetic testing
  • gut immunology
  • gut inflammation
  • growth factors
  • gut differentiation
  • gut hormones

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  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of Jichi-Ika University Hospital (Saitama, Japan) and Nagoya Central Hospital (Nagoya, Japan).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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