Reversion from Methionine Addiction to Methionine Independence Results in Loss of Tumorigenic Potential of Highly-malignant Lung-cancer Cells
Jun Yamamoto, YUSUKE AOKI, Qinghong Han, Norihiko Sugisawa, YU SUN, Kazuyuki Hamada, Hiroto Nishino, Sachiko Inubushi, Kentaro Miyake, Ryusei Matsuyama, Michael Bouvet, Itaru Endo, Robert M. Hoffman
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: , 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.