ArticleExperimental cell research2019
Targeting mitochondrial hexokinases increases efficacy of histone deacetylase inhibitors in solid tumor models.
Article in Experimental cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
9 citing papers in PubMed, 16 citations in OpenAlex.
- The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- The hexokinase "HKDC1" interaction with the mitochondria is essential for liver cancer progression.Cell death & disease · 2022Article
- Dual Inhibition of Histone Deacetylases and the Mechanistic Target of Rapamycin Promotes Apoptosis in Cell Line Models of Uveal Melanoma.Investigative ophthalmology & visual science · 2021Article
- Traditional Chinese medicine Bu-Shen-Jian-Pi-Fang attenuates glycolysis and immune escape in clear cell renal cell carcinoma: results based on network pharmacology.Bioscience reports · 2021Article
- Modulation of lactate-lysosome axis in dendritic cells by clotrimazole potentiates antitumor immunity.Journal for immunotherapy of cancer · 2021Article
- Hexokinase 3 dysfunction promotes tumorigenesis and immune escape by upregulating monocyte/macrophage infiltration into the clear cell renal cell carcinoma microenvironment.International journal of biological sciences · 2021Article
- Dioscin Inhibited Glycolysis and Induced Cell Apoptosis in Colorectal Cancer via Promoting c-myc Ubiquitination and Subsequent Hexokinase-2 Suppression.OncoTargets and therapy · 2020Article
- Histone Deacetylases and their Inhibitors in Cancer Epigenetics.Diseases (Basel, Switzerland) · 2019Review
- Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy.International journal of nanomedicine · 2019Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Hexokinase 1 and 2 have been shown to inhibit Bak- and Bax-mediated apoptosis, leading us to combine the histone deacetylase inhibitor romidepsin with clotrimazole or bifonazole, two compounds that reportedly decrease mitochondrial localization of hexokinases. Cancer cell lines derived from breast, kidney, lung, colon or ovarian cancers were treated with a short-term exposure to 25 ng/ml romidepsin combined with either clotrimazole or bifonazole. The combination of romidepsin with 25 µM clotrimazole or bifonazole resulted in increased annexin staining compared to cells treated with any of the drugs alone. Cell death was caspase-mediated, as the pan-caspase inhibitor Q-VD-OPh was found to inhibit apoptosis induced by the combination. A549 lung cancer cells or HCT-116 cells deficient in Bak and Bax were also resistant to apoptosis with the combination implicating the intrinsic apoptotic pathway. We found that a 24 h treatment with clotrimazole or bifonazole decreased total hexokinase 2 expression, resulting in a 76% or 60% decrease, respectively, of mitochondrial expression of hexokinase 2. Mitochondrial hexokinase 1 levels increased 2-fold or less. Our work suggests that the combination of a short-term romidepsin treatment with bifonazole or clotrimazole leads to increased apoptosis, most likely due to decreased mitochondrial expression of hexokinase 2.
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