Tetra-O-Methyl Nordihydroguaiaretic Acid Broadly Suppresses Cancer Metabolism and Synergistically Induces Strong Anticancer Activity in Combination with Etoposide, Rapamycin and UCN-01

PloS One
Kotohiko Kimura, Ru Chih C Huang

Abstract

The ability of Tetra-O-methyl nordihydroguaiaretic acid (M4N) to induce rapid cell death in combination with Etoposide, Rapamycin, or UCN-01 was examined in LNCaP cells, both in cell culture and animal experiments. Mice treated with M4N drug combinations with either Etoposide or Rapamycin showed no evidence of tumor and had a 100% survival rate 100 days after tumor implantation. By comparison all other vehicles or single drug treated mice failed to survive longer than 30 days after implantation. This synergistic improvement of anticancer effect was also confirmed in more than 20 cancer cell lines. In LNCaP cells, M4N was found to reduce cellular ATP content, and suppress NDUFS1 expression while inducing hyperpolarization of mitochondrial membrane potential. M4N-treated cells lacked autophagy with reduced expression of BNIP3 and ATG5. To understand the mechanisms of this anticancer activity of M4N, the effect of this drug on three cancer cell lines (LNCaP, AsPC-1, and L428 cells) was further examined via transcriptome and metabolomics analyses. Metabolomic results showed that there were reductions of 26 metabolites essential for energy generation and/or production of cellular components in common with these three cell lines foll...Continue Reading

References

Aug 1, 1973·Biochemical Pharmacology·R S PardiniD C Fletcher
Oct 1, 1970·Biochemical Pharmacology·R S PardiniD C Fletcher
Feb 15, 2000·The Journal of Biological Chemistry·B T ChuaP Li
Aug 5, 2000·Cell Biology and Toxicology·A VanellaM L Barcellona
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·T K Li, L F Liu
Apr 25, 2001·Journal of Chromatography. B, Biomedical Sciences and Applications·J D LambertR T Dorr
May 27, 2003·Apoptosis : an International Journal on Programmed Cell Death·J D LyA Lawen
Jul 25, 2003·Cancer Biology & Therapy·Shile HuangPeter J Houghton
Feb 24, 1956·Science·O WARBURG
Aug 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chih-Chuan ChangRu Chih C Huang
Sep 15, 2004·Molecular Aspects of Medicine·Jean-Paul BonnefontJean Bastin
Jun 17, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard ParkRu Chih C Huang
Sep 6, 2005·Genes & Development·Mi Young KimW Lee Kraus
Sep 26, 2006·Nature Cell Biology·Shida YousefiHans-Uwe Simon
Jan 20, 2007·The Journal of Clinical Investigation·Ravi K AmaravadiCraig B Thompson
Aug 22, 2007·Cell Biochemistry and Biophysics·Elmus G BealeClaude Forest
Nov 6, 2008·Expert Review of Anticancer Therapy·John P Fruehauf, Valerie Trapp
Dec 26, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Imran N MungrueAldons J Lusis
Feb 21, 2009·Cell Death and Differentiation·J Zhang, P A Ney
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
Mar 24, 2009·Journal of Molecular and Cellular Cardiology·Fabio Di Lisa, Paolo Bernardi
May 2, 2009·Cell Death and Differentiation·Y ChenS B Gibson
May 5, 2009·Autophagy·David C RubinszteinDaniel J Klionsky
Jun 23, 2009·Anti-cancer Agents in Medicinal Chemistry·Paolo RuzzaLuigi Quintieri
Jul 21, 2009·The Journal of Biological Chemistry·Juliette GafniLisa M Ellerby
Aug 26, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Matthew R ThompsonBryan R G Williams
Aug 27, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eileen White, Robert S DiPaola
Mar 17, 2010·Mitochondrion·Jared RutterJoshua D Schiffman
Oct 29, 2010·Nature·Shinichi YachidaChristine A Iacobuzio-Donahue
Nov 17, 2010·Cancer Letters·Alexander ArltHeiner Schäfer
Feb 4, 2011·American Journal of Physiology. Cell Physiology·Rebecca J BoohakerAnnette R Khaled
May 5, 2011·Molecular Interventions·Paul DentSteven Grant
Jun 18, 2011·Science·Jonathan S OakhillBruce E Kemp
Jul 5, 2011·Methods in Cell Biology·Donald WlodkowicZbigniew Darzynkiewicz
Sep 1, 2011·Nature Reviews. Drug Discovery·Matthew G Vander Heiden
Sep 10, 2011·Frontiers in Pharmacology·Paolo E PorporatoPierre Sonveaux
Dec 23, 2011·The Biochemical Journal·Jisun LeeJianhua Zhang
Jan 4, 2012·The Prostate·Lien SpansFrank Claessens
Feb 11, 2012·Neuro-oncology·Stuart A GrossmanUNKNOWN Adult Brain Tumor Consortium

❮ Previous
Next ❯

Citations

Sep 11, 2016·Journal of Industrial Microbiology & Biotechnology·Young Ji YooYeo Joon Yoon
Nov 2, 2017·Journal of Comparative Effectiveness Research·Beate JahnUwe Siebert
Jun 27, 2018·Antioxidants & Redox Signaling·Francesca GiampieriMaurizio Battino
Jun 16, 2017·Expert Opinion on Investigational Drugs·Matthew W McCarthy, Thomas J Walsh
Oct 10, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Angel ChaoChyong-Huey Lai
Feb 12, 2020·Molecular Medicine·Deze ZhaoHelei Hou
Jun 5, 2017·Drug Discovery Today·Robert C PeeryJian-Ting Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
Protein Assay
electrophoresis
PCR

Software Mentioned

Cufflinks
ensembl
Ensemble
Metabolon
Combosyn
Carl
TopHat

Related Concepts

Related Feeds

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Cancer Metabolic Reprogramming

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Cancer Metabolism: Therapeutic Targets

Targeting the mechanisms by which cancer cells acquire energy for metabolic needs is a therapeutic target. Discover the latest research on cancer metabolism and therapeutic targets.

Cancer Metabolic Reprogramming (Keystone)

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.