RT Journal Article SR Electronic T1 Reversion from Methionine Addiction to Methionine Independence Results in Loss of Tumorigenic Potential of Highly-malignant Lung-cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 641 OP 643 DO 10.21873/anticanres.14815 VO 41 IS 2 A1 JUN YAMAMOTO A1 YUSUKE AOKI A1 QINGHONG HAN A1 NORIHIKO SUGISAWA A1 YU SUN A1 KAZUYUKI HAMADA A1 HIROTO NISHINO A1 SACHIKO INUBUSHI A1 KENTARO MIYAKE A1 RYUSEI MATSUYAMA A1 MICHAEL BOUVET A1 ITARU ENDO A1 ROBERT M. HOFFMAN YR 2021 UL http://ar.iiarjournals.org/content/41/2/641.abstract 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.