ArticleJournal of experimental & clinical cancer research : CR2016
Non-benzoquinone geldanamycin analogs trigger various forms of death in human breast cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- Peptomer Linkers Enable Kinetic Control over Co-Delivery of Multiple Chemotherapeutics.Advanced healthcare materials · 2026Article
- Cell Death: Mechanisms and Potential Targets in Breast Cancer Therapy.International journal of molecular sciences · 2024Review
- Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis.Journal of pharmaceutical analysis · 2024Article
- Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.Acta pharmaceutica Sinica. B · 2024Review
- An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil's Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer.Molecules (Basel, Switzerland) · 2023Article
- Prognostic Lysosome-Related Biomarkers for Predicting Drug Candidates in Hepatocellular Carcinoma: An Insilco Analysis.Journal of hepatocellular carcinoma · 2023Article
- HSP90 mediates the connection of multiple programmed cell death in diseases.Cell death & disease · 2022Review
- Necroptosis: A Pathogenic Negotiator in Human Diseases.International journal of molecular sciences · 2022Review
- The Role of Protein S-Nitrosylation in Protein Misfolding-Associated Diseases.Life (Basel, Switzerland) · 2021Review
- The potential role of necroptosis in clinical diseases (Review).International journal of molecular medicine · 2021Review
- Reblastatins Inhibit Phenotypic Changes of Monocytes/Macrophages in a Milieu Rich in 27-Hydroxycholesterol.Immune network · 2020Article
- Current translational potential and underlying molecular mechanisms of necroptosis.Cell death & disease · 2019Review
- Bishonokiol A inhibits breast cancer cell invasion and migration by suppressing hypoxia inducible factor-1α.Journal of bioenergetics and biomembranes · 2019Article
- Hydrogen Sulfide Gas Exposure Induces Necroptosis and Promotes Inflammation through the MAPK/NF-Oxidative medicine and cellular longevity · 2019Article
- Article
- Production of bone mineral material and BMP-2 in osteoblasts cultured on double acid-etched titanium.Medicina oral, patologia oral y cirugia bucal · 2017Article
- Shikonin induces necroptosis by reactive oxygen species activation in nasopharyngeal carcinoma cell line CNE-2Z.Journal of bioenergetics and biomembranes · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHsp90 proteins are important therapeutic targets for many anti-cancer drugs in clinical trials. Geldanamycin (GA) was identified as the first natural inhibitor of Hsp90, increasing evidence suggests that GA was not a good choice for clinical trials. In this study, we investigated two new non-benzoquinone geldanamycin analogs of Hsp90 inhibitors, DHQ3 and 17-demethoxy-reblastatin (17-DR), to explore the molecular mechanisms of their anti-cancer activity in vivo and vitro.
methodsMTT and colony formation assays were used to measure cell viability. Flow cytometry, DAPI staining, ATP assay, electron microscopy, western blots, siRNAs transfection and immunofluorescence were used to determine the molecular mechanism of DHQ3- or 17-DR-induced different forms of death in human breast cancer MDA-MB-231 cells. Malachite green reagent was used to measure ATPase activity of the analogs.
resultsDHQ3 and 17-DR presented efficiently inhibitory effect in MDA-MB-231 cell lines, and DHQ3 induced necroptosis by activation of the RIP1-RIP3-MLKL necroptosis cascade. And DHQ3-induced cell death was inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), but not by a caspase inhibitor z-VAD-fmk. On the other hand, 17-DR induced apoptosis in MDA-MB-231 cells, indicating a caspase-dependent killing mechanism. We further demonstrated that down-regulation of RIP1 and RIP3 by siRNA protected against DHQ3 but not 17-DR induced cell death. These results were confirmed by electron microscopy. DHQ3 and 17-DR induced the degradation of Hsp90 client proteins, and they showed strong antitumor effects in MDA-MB-231 cell-xenografted nude mice.
conclusionsThese findings supported that DHQ3 and 17-DR induce different forms of death in some cancer cell line via activation of different pathways. All of the results provided evidence for its anti-tumorigentic action with low hepatotoxicity in vivo, making them promising anti-breast cancer agents.
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