ArticleExperimental hematology2008
R-(-)-gossypol (AT-101) activates programmed cell death in multiple myeloma cells.
Article in Experimental hematology, 2008. 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 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.
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, 62 citations in OpenAlex.
- A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors.Investigational new drugs · 2020Trial
- An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2009Trial
- Stalling the Enemy: Targeting Nsp13 for Next-Generation SARS-CoV-2 Antivirals.International journal of molecular sciences · 2026Article
- Review
- AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma.Cancers · 2023Article
- Molecular docking analysis of MCL-1 inhibitors for breast cancer management.Bioinformation · 2023Article
- Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.Pharmaceutics · 2022Review
- Updates in the Use of BCL-2-Family Small Molecule Inhibitors for the Treatment of Relapsed/Refractory Multiple Myeloma.Cancers · 2022Review
- An Overview of Cotton Gland Development and Its Transcriptional Regulation.International journal of molecular sciences · 2022Review
- Root Illumination Promotes Seedling Growth and Inhibits Gossypol Biosynthesis in Upland Cotton.Plants (Basel, Switzerland) · 2022Article
- Cyclic RGD-Decorated Liposomal Gossypol AT-101 Targeting for Enhanced Antitumor Effect.International journal of nanomedicine · 2022Article
- Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma.Cells · 2021Review
- Review
- Cotton roots are the major source of gossypol biosynthesis and accumulation.BMC plant biology · 2020Article
- Gossypol induces apoptosis of multiple myeloma cells through the JUN-JNK pathway.American journal of cancer research · 2020Article
- Smac mimetic LCL161 overcomes protective ER stress induced by obatoclax, synergistically causing cell death in multiple myeloma.Oncotarget · 2016Article
- Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation.Frontiers in pediatrics · 2016Review
- Treatment Strategies that Enhance the Efficacy and Selectivity of Mitochondria-Targeted Anticancer Agents.International journal of molecular sciences · 2015Review
- AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenström macroglobulinaemia.British journal of haematology · 2014Article
- Proteomic analysis of gossypol induces necrosis in multiple myeloma cells.BioMed research international · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveBcl-2 family proteins play a critical role in malignancies by regulating the balance between cell survival and apoptosis. R-(-)-gossypol (AT-101) is a small molecule that mimics the BH3 domain of cellular Bcl-2 inhibitors and interferes with the function of prosurvival Bcl-2 proteins. We examined the cytotoxicity of AT-101 in the context of multiple myeloma, a fatal hematological malignancy. MATERIALS AND
methodsMultiple myeloma cell lines and primary cells obtained from multiple myeloma patients were used to investigate the effects of AT-101. Cell viability, apoptosis, and apoptosis pathways were examined using conventional viability assays, flow cytometry, and immunoblots.
resultsAT-101 was not only cytotoxic to conventional multiple myeloma cell lines, but was also effective against drug-resistant cell lines and primary multiple myeloma patient cells. Furthermore, AT-101 decreased proliferation of multiple myeloma cell lines in the presence of marrow stromal cells, indicating that this drug may overcome the protective effect of the microenvironment that is important for multiple myeloma cell proliferation and survival. Apoptosis was activated via the mitochondrial pathway in multiple myeloma cell lines treated with AT-101 as demonstrated by an increased Bax to Bcl-2 ratio, mitochondrial membrane depolarization, and caspase activation. Finally, our studies demonstrated that AT-101 exhibits potent synergy with dexamethasone, a valuable therapeutic for multiple myeloma.
conclusionThese data suggest that the activity of AT-101 may be highly relevant to multiple myeloma disease biology and may represent an option for treatment of patients with this disease.
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Registered trials
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