Accelerated lipid catabolism and autophagy are cancer survival mechanisms under inhibited glutaminolysis

Cancer Letters
Anna HalamaKarsten Suhre

Abstract

Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy. Simultaneously inhibiting glutaminolysis and either beta oxidation with trimetazidine or autophagy with chloroquine both induced cancer cell death. Here we identified metabolic escape mechanisms contributing to cancer cell survival under treatment and we suggest potentially translational strategy for combined cancer therapy, given that chloroquine is an FDA approved drug. Our findings are first to show efficiency of combined inhibition of glutaminolysis and beta oxidation as potential anti-cancer strategy as well as add to the evidence that combined inhibition of glutaminolysis and autophagy may be effective in g...Continue Reading

Citations

Dec 28, 2019·Journal of Clinical Medicine·Alessandro Di MinnoElena Tremoli
Mar 11, 2020·Biomolecules·Piotr WójcikElżbieta Skrzydlewska
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Yangchun XieDaolin Tang
Feb 17, 2019·Archives of Pharmacal Research·Min-Kyue Shin, Jae-Ho Cheong
Jul 19, 2020·Archives of Toxicology·José M MatésJavier Márquez
May 16, 2019·Metabolomics : Official Journal of the Metabolomic Society·Andreas MockChristel Herold-Mende
Sep 4, 2020·Cancers·Lydie M O BarbeauKasper M A Rouschop
Feb 5, 2021·International Journal of Molecular Sciences·Duc-Vinh Pham, Pil-Hoon Park
Feb 13, 2021·Metabolites·Anna HalamaTatiana Vinardell
Feb 19, 2021·IScience·Hanne-Line RabbenChun-Mei Zhao
Oct 27, 2021·Cancer Biology & Therapy·Vinod S BishtKiran Ambatipudi
Dec 19, 2021·Clinical & Experimental Metastasis·Sara Abdul KaderAnna Halama

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

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.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

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.

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

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

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.

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 & 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.