ArticleMolecular cancer therapeutics2008
Natural BH3 mimetic (-)-gossypol chemosensitizes human prostate cancer via Bcl-xL inhibition accompanied by increase of Puma and Noxa.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 184 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
- A Phase II Study of AT-101 to Overcome Bcl-2--Mediated Resistance to Androgen Deprivation Therapy in Patients With Newly Diagnosed Castration-Sensitive Metastatic Prostate Cancer.Clinical genitourinary cancer · 2016Trial
- A validated HPLC assay for the determination of R-(-)-gossypol in human plasma and its application in clinical pharmacokinetic studies.Journal of pharmaceutical and biomedical analysis · 2012Trial
- 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
- Gossypol improves myocardial dysfunction caused by sepsis by regulating histone acetylation.Clinical and translational science · 2023Article
- Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight.International journal of molecular sciences · 2023Review
- Advances in the study of aerobic glycolytic effects in resistance to radiotherapy in malignant tumors.PeerJ · 2023Review
- Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.Pharmaceutics · 2022Review
- In Vitro Anticancer Activity of Two Ferrocene-Containing Camphor Sulfonamides as Promising Agents against Lung Cancer Cells.Biomedicines · 2022Article
- Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials.Pharmaceuticals (Basel, Switzerland) · 2022Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- The SMAC mimetic AT-101 exhibits anti-tumor and anti-metastasis activity in lung adenocarcinoma cells by the IAPs/ caspase-dependent apoptosis and p65-NFƙB cross-talk.Iranian journal of basic medical sciences · 2021Article
- Biomimetic Approaches to the Synthesis of Natural Disesquiterpenoids: An Update.Plants (Basel, Switzerland) · 2021Review
- Review
- Review
- Prostate cancer: Therapeutic prospect with herbal medicine.Current research in pharmacology and drug discovery · 2021Review
- Harnessing Lactate Metabolism for Radiosensitization.Frontiers in oncology · 2021Review
- Targeting Protein Neddylation to Inactivate Cullin-RING Ligases by Gossypol: A Lucky Hit or a New Start?Drug design, development and therapy · 2021Review
- Design, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2.International journal of molecular sciences · 2020Article
- Pharmacological inhibition of androgen receptor expression induces cell death in prostate cancer cells.Cellular and molecular life sciences : CMLS · 2020Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Antiapoptotic members of the Bcl-2 family proteins are overexpressed in prostate cancer and are promising molecular targets for modulating chemoresistance of prostate cancer. (-)-Gossypol, a natural BH3 mimetic, is a small-molecule inhibitor of Bcl-2/Bcl-xL/Mcl-1 currently in phase II clinical trials as an adjuvant therapy for human prostate cancer. Our objective is to examine the chemosensitization potential of (-)-gossypol in prostate cancer and its molecular mechanisms of action. (-)-Gossypol inhibited cell growth and induced apoptosis through mitochondria pathway in human prostate cancer PC-3 cells and synergistically enhanced the antitumor activity of docetaxel both in vitro and in vivo in PC-3 xenograft model in nude mouse. (-)-Gossypol blocked the interactions of Bcl-xL with Bax or Bad in cancer cells by fluorescence resonance energy transfer assay and overcame the Bcl-xL protection of FL5.12 model cells on interleukin-3 withdrawal. Western blot and real-time PCR studies showed that a dose-dependent increase of the proapoptotic BH3-only proteins Noxa and Puma contributed to the cell death induced by (-)-gossypol and to the synergistic effects of (-)-gossypol and docetaxel. The small interfering RNA knockdown studies showed that Noxa and Puma are required in the (-)-gossypol-induced cell death. Taken together, these data suggest that (-)-gossypol exerts its antitumor activity through inhibition of the antiapoptotic protein Bcl-xL accompanied by an increase of proapoptotic Noxa and Puma. (-)-Gossypol significantly enhances the antitumor activity of chemotherapy in vitro and in vivo, representing a promising new regime for the treatment of human hormone-refractory prostate cancer with Bcl-2/Bcl-xL/Mcl-1 overexpression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.