Journal Article

Reversion from Methionine Addiction to Methionine Independence Results in Loss of Tumorigenic Potential of Highly-malignant Lung-cancer Cells

HOFFMAN, ROBERT M., HAN, QINGHONG, NISHINO, HIROTO, INUBUSHI, SACHIKO, YAMAMOTO, JUN, SUN, YU, BOUVET, MICHAEL, MATSUYAMA, RYUSEI, SUGISAWA, NORIHIKO, MIYAKE, KENTARO, HAMADA, KAZUYUKI, ENDO, ITARU, AOKI, YUSUKE

2021

Overview

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. Methionine-addicted H460 parental cancer cells and methionine-independent revertant H460-R1 cells were injected in nude mice subcutaneously. When the parental H460 methionine-addicted cells were injected in nude mice at 2.5×10 , 1×10 and 5×10 , 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. There is a tight linkage between methionine addiction and malignancy.

• Publisher: International Institute of Anticancer Research
• Subject: Addictions / Animals / Cancer / Cell cycle / Cell Line, Tumor / Cell Proliferation / Cell Transformation, Neoplastic - metabolism / Cell Transformation, Neoplastic - pathology / Fibroblasts / Humans / Lung cancer / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Lungs / Malignancy / Medical research / Metabolism / Methionine / Methionine - metabolism / Mice / Mice, Nude / Signal Transduction / Tumor Burden / Tumors