ArticleFree radical biology & medicine2013
Aldose reductase inhibition enhances TRAIL-induced human colon cancer cell apoptosis through AKT/FOXO3a-dependent upregulation of death receptors.
Article in Free radical biology & medicine, 2013. 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, 45 citations in OpenAlex.
- FOXO3a upregulates DNA repair activities by transcriptional activation of target genes and provides the resistance to gamma radiation and the extension of lifespan in mouse.Biogerontology · 2025Article
- Exploring the Molecular Mechanism of 1,25(OH)Current issues in molecular biology · 2025Article
- AMPK Alchemy: Therapeutic Potentials in Allergy, Aging, and Cancer.Biomolecules & therapeutics · 2024Review
- Aldo-keto reductases: Role in cancer development and theranostics.Oncology research · 2024Review
- Article
- FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Transcription factors in colorectal cancer: molecular mechanism and therapeutic implications.Oncogene · 2021Review
- Aldo Keto Reductases AKR1B1 and AKR1B10 in Cancer: Molecular Mechanisms and Signaling Networks.Advances in experimental medicine and biology · 2021Review
- Alternol Sensitizes Renal Carcinoma Cells to TRAIL-Induced Apoptosis.Frontiers in pharmacology · 2021Article
- Role of aldo-keto reductase family 1 member B1 (AKR1B1) in the cancer process and its therapeutic potential.Journal of cellular and molecular medicine · 2020Review
- The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis.Molecular cancer · 2019Review
- HDAC4 degradation by combined TRAIL and valproic acid treatment induces apoptotic cell death of TRAIL-resistant head and neck cancer cells.Scientific reports · 2018Article
- Critical role of FOXO3a in carcinogenesis.Molecular cancer · 2018Review
- Aldose reductase inhibitor, fidarestat prevents doxorubicin-induced endothelial cell death and dysfunction.Biochemical pharmacology · 2018Article
- Aldose reductase inhibitor increases doxorubicin-sensitivity of colon cancer cells and decreases cardiotoxicity.Scientific reports · 2017Article
- Assessment of histone tail modifications and transcriptional profiling during colon cancer progression reveals a global decrease in H3K4me3 activity.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra.Current genomics · 2017Review
- Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo.Oncotarget · 2016Article
- Epalrestat increases intracellular glutathione levels in Schwann cells through transcription regulation.Redox biology · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
One of the major problems associated with the chemotherapy of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) that selectively kills tumor cells is decreased drug resistance. This warranted the development of safe novel pharmacological agents that could sensitize the tumor cells to TRAIL. Herein, we examined the role of aldose reductase (AR) in sensitizing cancer cells to TRAIL and potentiating TRAIL-induced apoptosis of human colon cancer cells. We demonstrate that AR inhibition potentiates TRAIL-induced cytotoxicity in cancer cells by upregulation of both death receptor (DR)-5 and DR4. Knockdown of DR5 and DR4 significantly (>85%) reduced the sensitizing effect of the AR inhibitor fidarestat on TRAIL-induced apoptosis. Further, AR inhibition also downregulates cell survival proteins (Bcl-xL, Bcl-2, survivin, XIAP, and FLIP) and upregulates the expression of proapoptotic proteins such as Bax and alters mitochondrial membrane potential, leading to cytochrome c release, caspases-3 activation, and PARP cleavage. We found that AR inhibition regulates AKT/PI3K-dependent activation of forkhead transcription factor FOXO3a. Knockdown of FOXO3a significantly (>80%) abolished AR inhibition-induced upregulation of DR5 and DR4 and apoptosis in colon cancer cells. Overall, our results show that fidarestat potentiates TRAIL-induced apoptosis through downregulation of cell survival proteins and upregulation of death receptors via activation of the AKT/FOXO3a pathway.
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