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Research ArticleExperimental Studies

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 and ROBERT M. HOFFMAN
Anticancer Research February 2021, 41 (2) 641-643; DOI: https://doi.org/10.21873/anticanres.14815
JUN YAMAMOTO
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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  • For correspondence: all@anticancer.com endoit@yokohama-cu.ac.jp jun.ymmt.1014@gmail.com
YUSUKE AOKI
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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QINGHONG HAN
1AntiCancer Inc, San Diego, CA, U.S.A.;
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NORIHIKO SUGISAWA
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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YU SUN
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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KAZUYUKI HAMADA
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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HIROTO NISHINO
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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SACHIKO INUBUSHI
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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KENTARO MIYAKE
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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RYUSEI MATSUYAMA
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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MICHAEL BOUVET
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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ITARU ENDO
3Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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  • For correspondence: all@anticancer.com endoit@yokohama-cu.ac.jp jun.ymmt.1014@gmail.com
ROBERT M. HOFFMAN
1AntiCancer Inc, San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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  • For correspondence: all@anticancer.com endoit@yokohama-cu.ac.jp jun.ymmt.1014@gmail.com
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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.

Key Words:
  • Cancer
  • methionine addiction
  • reversion
  • methionine independence
  • tumorigenicity
  • lung cancer
  • H460

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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Anticancer Research: 41 (2)
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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
Anticancer Research Feb 2021, 41 (2) 641-643; DOI: 10.21873/anticanres.14815

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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
Anticancer Research Feb 2021, 41 (2) 641-643; DOI: 10.21873/anticanres.14815
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Keywords

  • Cancer
  • methionine addiction
  • reversion
  • methionine independence
  • tumorigenicity
  • lung cancer
  • H460
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