ArticleThe Prostate2019
Alternol eliminates excessive ATP production by disturbing Krebs cycle in prostate cancer.
Article in The Prostate, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Alternol-Induced Oxidative Modification of SQSTM1/p62 Is Associated with Nrf2 Signaling and Autophagy-Related Responses in Prostate Cancer Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Citric Acid Cycle Genes and Nutrigenetics.International journal of molecular sciences · 2026Review
- Alternol inhibits GAPDH activity and disrupts glycolytic flux preferentially in cancer cells.Frontiers in pharmacology · 2026Article
- Components of the Endosome-Lysosome Vesicular Machinery as Drivers of the Metastatic Cascade in Prostate Cancer.Cancers · 2024Review
- Identification ofJournal of gastrointestinal oncology · 2024Article
- Establishment of a prognostic risk model for prostate cancer based on Gleason grading and cuprotosis related genes.Journal of cancer research and clinical oncology · 2024Article
- Natural compound Alternol exerts a broad anti-cancer spectrum and a superior therapeutic safety indexFrontiers in pharmacology · 2024Article
- A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferaseOncology research · 2024Article
- Natural compound Alternol actives multiple endoplasmic reticulum stress-responding pathways contributing to cell death.Frontiers in pharmacology · 2024Article
- Current Understanding of Androgen Signaling in Prostatitis and its Treatment: A Review.Current medicinal chemistry · 2024Review
- Progress in the research of cuproptosis and possible targets for cancer therapy.World journal of clinical oncology · 2023Review
- Unraveling the Peculiar Features of Mitochondrial Metabolism and Dynamics in Prostate Cancer.Cancers · 2023Review
- Article
- Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein.Cell death & disease · 2022Article
- Epigallocatechin gallate triggers apoptosis by suppressing de novo lipogenesis in colorectal carcinoma cells.FEBS open bio · 2022Article
- Bortezomib potentiates antitumor activity of mitoxantrone through dampening Wnt/β-catenin signal pathway in prostate cancer cells.BMC cancer · 2021Article
- The therapeutic potential of mitochondrial toxins.The Journal of antibiotics · 2021Review
- Molecular Basis of Prostate Cancer and Natural Products as Potential Chemotherapeutic and Chemopreventive Agents.Frontiers in pharmacology · 2021Review
- Alternol triggers immunogenic cell deathOncoimmunology · 2021Article
- A Prognostic Model for Brain Glioma Patients Based on 9 Signature Glycolytic Genes.BioMed research international · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAlternol is a natural compound isolated from fermentation products of a mutant fungus. Our previous studies demonstrated that Alternol specifically kills cancer cells but spares benign cells.
methodsTo investigate the mechanism underlying alternol-induced cancer cell-specific killing effect, we took a comprehensive strategy to identify Alternol's protein targets in prostate cancer cells, including PC-3, C4-2, and 22RV1, plus benign BPH1 cell lines. Major experimental techniques included biotin-streptavidin pulldown assay coupled with mass-spectrometry, in vitro enzyme activity assay for Krebs cycle enzymes and gas chromatography-mass spectrometry (GC-MS) for metabolomic analysis.
resultsAmong 14 verified protein targets, four were Krebs cycle enzymes, fumarate hydratase (FH), malate dehydrogenase-2 (MDH2), dihydrolipoamide acetyltransferase (DLAT) in pyruvate dehydrogenase complex (PDHC) and dihydrolipoamide S-succinyltransferase (DLST) in a-ketoglutarate dehydrogenase complex (KGDHC). Functional assays revealed that PDHC and KGDHC activities at the basal level were significantly higher in prostate cancer cells compared to benign prostate BPH1 cells, while alternol treatment reduced their activities in cancer cells close to the levels in BPH1 cells. Although FH and MDH2 activities were comparable among prostate cancer and benign cell lines at the basal level, Alternol treatment largely increased their activities in cancer cells. Metabolomic analysis revealed that Alternol treatment remarkably reduced the levels of malic acid, fumaric acid, and isocitric acid and mitochondrial respiration in prostate cancer cells. Alternol also drastically reduced mitochondrial respiration and ATP production in PC-3 cells in vitro or in xenograft tissues but not in BPH1 cells or host liver tissues.
conclusionsAlternol interacts with multiple Krebs cycle enzymes, resulting in reduced mitochondrial respiration and ATP production in prostate cancer cells and xenograft tissues, providing a novel therapeutic strategy for prostate cancer treatment.
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Registered trials
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