Jun Yamamoto1,2,3, Yusuke Aoki4,2, Qinghong Han4, Norihiko Sugisawa4,2, Y U Sun4,2, Kazuyuki Hamada4,2, Hiroto Nishino4,2, Sachiko Inubushi4,2, Kentaro Miyake3, Ryusei Matsuyama3, Michael Bouvet2, Itaru Endo5, Robert M Hoffman1,2. 1. AntiCancer Inc, San Diego, CA, U.S.A.; all@anticancer.com endoit@yokohama-cu.ac.jp jun.ymmt.1014@gmail.com. 2. Department of Surgery, University of California, San Diego, CA, U.S.A. 3. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 4. AntiCancer Inc, San Diego, CA, U.S.A. 5. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan all@anticancer.com endoit@yokohama-cu.ac.jp jun.ymmt.1014@gmail.com.
Abstract
BACKGROUND/AIM: Methionine addiction, a fundamental and general hallmark of cancer, is due to the excess use of methionine for transmethylation, and is described as the Hoffman-effect. Methionine-addicted cancer cells can revert at low frequency to methionine independence when selected under methionine-restriction. We report here that highly-malignant methionine-addicted H460 human lung-cancer cells, when selected for methionine independence, have greatly-reduced tumorigenic potential. MATERIALS AND METHODS: Methionine-addicted H460 parental cancer cells and methionine-independent revertant H460-R1 cells were injected in nude mice subcutaneously. RESULTS: When the parental H460 methionine-addicted cells were injected in nude mice at 2.5×105, 1×105 and 5×104, the cells could form tumors. In contrast, the H460-R1 methionine-independent revertant cells could not form tumors when the above-listed cell numbers were injected in nude mice. CONCLUSION: There is a tight linkage between methionine addiction and malignancy.
BACKGROUND/AIM: Methionine addiction, a fundamental and general hallmark of cancer, is due to the excess use of methionine for transmethylation, and is described as the Hoffman-effect. Methionine-addicted cancer cells can revert at low frequency to methionine independence when selected under methionine-restriction. We report here that highly-malignant methionine-addicted H460 humanlung-cancer cells, when selected for methionine independence, have greatly-reduced tumorigenic potential. MATERIALS AND METHODS:Methionine-addicted H460 parental cancer cells and methionine-independent revertant H460-R1 cells were injected in nude mice subcutaneously. RESULTS: When the parental H460 methionine-addicted cells were injected in nude mice at 2.5×105, 1×105 and 5×104, the cells could form tumors. In contrast, the H460-R1methionine-independent revertant cells could not form tumors when the above-listed cell numbers were injected in nude mice. CONCLUSION: There is a tight linkage between methionine addiction and malignancy.