PT - JOURNAL ARTICLE AU - JUN YAMAMOTO AU - YUSUKE AOKI AU - QINGHONG HAN AU - NORIHIKO SUGISAWA AU - YU SUN AU - KAZUYUKI HAMADA AU - HIROTO NISHINO AU - SACHIKO INUBUSHI AU - KENTARO MIYAKE AU - RYUSEI MATSUYAMA AU - MICHAEL BOUVET AU - ITARU ENDO AU - ROBERT M. HOFFMAN TI - Reversion from Methionine Addiction to Methionine Independence Results in Loss of Tumorigenic Potential of Highly-malignant Lung-cancer Cells AID - 10.21873/anticanres.14815 DP - 2021 Feb 01 TA - Anticancer Research PG - 641--643 VI - 41 IP - 2 4099 - http://ar.iiarjournals.org/content/41/2/641.short 4100 - http://ar.iiarjournals.org/content/41/2/641.full SO - Anticancer Res2021 Feb 01; 41 AB - 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.