ArticleCell cycle (Georgetown, Tex.)2016
GSH-dependent antioxidant defense contributes to the acclimation of colon cancer cells to acidic microenvironment.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Doxorubicin-Incorporated Nanoparticles Composed of Ce6-Conjugated Hyaluronic Acid-International journal of molecular sciences · 2026Article
- Acidosis and the role of nanotechnology in mitigating cancer progression.Oncology reviews · 2026Review
- Autophagic flux-lipid droplet biogenesis cascade sustains mitochondrial fitness in colorectal cancer cells adapted to acidosis.Cell death discovery · 2025Article
- PFKL Inhibition by DT-13: A Novel Approach to Combat Hepatocellular Carcinoma.International journal of hepatology · 2025Article
- IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment.iScience · 2023Article
- SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase.Cell death & disease · 2023Article
- Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach.Pharmaceutics · 2022Article
- Enhanced pentose phosphate pathway activity promotes pancreatic ductal adenocarcinoma progression via activating YAP/MMP1 axis under chronic acidosis.International journal of biological sciences · 2022Article
- A Prognostic Model for Colon Adenocarcinoma Patients Based on Ten Amino Acid Metabolism Related Genes.Frontiers in public health · 2022Article
- Inhibition of Mitochondrial Metabolism Leads to Selective Eradication of Cells Adapted to Acidic Microenvironment.International journal of molecular sciences · 2021Article
- Identification of m6A-Related Biomarkers Associated with Prognosis of Colorectal Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Autophagic Flux Unleashes GATA4-NF-Oxidative medicine and cellular longevity · 2021Article
- Perspectives on the Role of Isoliquiritigenin in Cancer.Cancers · 2021Review
- Effects and mechanisms of fatty acid metabolism‑mediated glycolysis regulated by betulinic acid‑loaded nanoliposomes in colorectal cancer.Oncology reports · 2020Article
- Effect of Flow-Induced Shear Stress in Nanomaterial Uptake by Cells: Focus on Targeted Anti-Cancer Therapy.Cancers · 2020Review
- Chromatin accessibility changes are associated with enhanced growth and liver metastasis capacity of acid-adapted colorectal cancer cells.Cell cycle (Georgetown, Tex.) · 2019Article
- Acidosis enhances the self-renewal and mitochondrial respiration of stem cell-like glioma cells through CYP24A1-mediated reduction of vitamin D.Cell death & disease · 2019Article
- ENO1 Acts as a Prognostic Biomarker Candidate and Promotes Tumor Growth and Migration Ability Through the Regulation of Rab1A in Colorectal Cancer.Cancer management and research · 2019Article
- Astrocytes induce proliferation of oligodendrocyte progenitor cells via connexin 47-mediated activation of the ERK/Id4 pathway.Cell cycle (Georgetown, Tex.) · 2017Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to increased glycolysis and poor local perfusion, solid tumors are usually immersed in an acidic microenvironment. While extracellular acidosis is cytotoxic, cancer cells eventually become acclimated to it. While previous studies have addressed the acute effect of acidosis on cancer cells, little is known about how cancer cells survive chronic acidosis. In this study we exposed colorectal cancer (CRC) cells (HCT15, HCT116 and LoVo) to acidic pH (pH 6.5) continuously for over three months and obtained CRC cells that become acclimated to acidic pH, designated as CRC-acidosis-acclimated or CRC-AA. We unexpectedly found that while acute exposure to low pH resulted in an increase in the level of intracellular reactive oxygen species (ROS), CRC-AA cells exhibited a significantly reduced level of ROS when compared to ancestor cells. CRC-AA cells were found to maintain a higher level of reduced glutathione, via the upregulation of CD44 and glutathione reductase (GSR), among others, than their ancestor cells. Importantly, CRC-AA cells were more sensitive to agents that deplete GSH. Moreover, downregulation of GSR by RNA interference was more deleterious to CRC-AA cells than to control cells. Together, our results demonstrate a critical role of glutathione-dependent antioxidant defense in acclimation of CRC cells to acidic extracellular pH.
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