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.
Footnotes
Authors’ Contributions
JY. and RMH designed and performed experiments and wrote the paper; QH, NS, YS, KH, YA, HN SI, KM, RM and MB gave technical support and conceptual advice. Writing, review, and/or revision of the manuscript: JY, IE and RMH.
Conflicts of Interest
JY, NS, YS, SI, KH, HN, YA, SI and RMH are or were unsalaried associates of AntiCancer Inc. QH is an employee of AntiCancer Inc. The Authors declare that there are no potential conflicts of interest regarding this study.
Funding
This work was supported in part by a Yokohama City University research grant “KAMOME Project” and in part by the Robert M. Hoffman Foundation for Cancer Research. Neither organization had a role in the design, execution, interpretation, or writing of the study.
- Received December 11, 2020.
- Revision received December 22, 2020.
- Accepted December 23, 2020.
- Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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