ArticleMolecular cancer therapeutics2011
(-)-Gossypol suppresses the growth of human prostate cancer xenografts via modulating VEGF signaling-mediated angiogenesis.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Phytochemicals in Inhibition of Prostate Cancer: Evidence from Molecular Mechanisms Studies.Biomolecules · 2022Pooled it
- Targeting protein-protein interactions in the BCL-2 family: opportunities for precision oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Targeting the Tumor Immune Microenvironment in Triple-Negative Breast Cancer: The Promise of Polyphenols.Cancers · 2025Review
- Aerobic glycolysis of vascular endothelial cells: a novel perspective in cancer therapy.Molecular biology reports · 2024Review
- Bcl-2 pathway inhibition in solid tumors: a review of clinical trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Pharmacotherapeutic Potential ofPharmaceutics · 2023Review
- Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages.Biomolecules · 2023Article
- Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.Pharmaceutics · 2022Review
- Identification ofMolecules (Basel, Switzerland) · 2022Article
- Preclinical Efficacy and Toxicity Analysis of the Pan-Histone Deacetylase Inhibitor Gossypol for the Therapy of Colorectal Cancer or Hepatocellular Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Gossypol decreased cell viability and down-regulated the expression of a number of genes in human colon cancer cells.Scientific reports · 2021Article
- Endothelial Cell Glucose Metabolism and Angiogenesis.Biomedicines · 2021Review
- Prostate cancer: Therapeutic prospect with herbal medicine.Current research in pharmacology and drug discovery · 2021Review
- Molecular mechanism of gossypol mediating CCL2 and IL‑8 attenuation in triple‑negative breast cancer cells.Molecular medicine reports · 2020Article
- Effects of gossypol on apoptosis‑related gene expression in racially distinct triple‑negative breast cancer cells.Oncology reports · 2019Article
- Isolation of Cottonseed Extracts That Affect Human Cancer Cell Growth.Scientific reports · 2018Article
- Effect of the BH3 Mimetic Polyphenol (-)-Gossypol (AT-101) on theFrontiers in pharmacology · 2018Article
- Comparison of region-of-interest-averaged and pixel-averaged analysis of DCE-MRI data based on simulations and pre-clinical experiments.Physics in medicine and biology · 2017Article
- Gossypol has anti-cancer effects by dual-targeting MDM2 and VEGF in human breast cancer.Breast cancer research : BCR · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
(-)-Gossypol, a natural BH3-mimetic and small-molecule Bcl-2 inhibitor, shows promise in ongoing phase II clinical trials for human cancers. However, whether (-)-gossypol plays functional roles in tumor angiogenesis has not been directly elucidated yet. In this study, we showed that (-)-gossypol dose dependently inhibited the expression of VEGF, Bcl-2, and Bcl-xL in human prostate cancer cells (PC-3 and DU 145) and primary cultured human umbilical vascular endothelial cells (HUVEC) in vitro. Notably, the growth of human prostate tumor PC-3 xenografts in mice was significantly suppressed by (-)-gossypol at a dosage of 15 mg/kg/d. This inhibitory action of (-)-gossypol in vivo was largely dependent on suppression of angiogenesis in the solid tumors, where VEGF expression and microvessel density were remarkably decreased. Furthermore, (-)-gossypol inhibited VEGF-induced chemotactic motility and tubulogenesis in HUVECs and human microvascular endothelial cells and suppressed microvessel sprouting from rat aortic rings ex vivo. When examined for the mechanism, we found that (-)-gossypol blocked the activation of VEGF receptor 2 kinase with the half maximal inhibitory concentration of 2.38 μmol/L in endothelial cells. Consequently, the phosphorylation of key intracellular proangiogenic kinases induced by VEGF was all suppressed by the treatment, such as Src family kinase, focal adhesion kinase, extracellular signal-related kinase, and AKT kinase. Taken together, the present study shows that (-)-gossypol potently inhibits human prostate tumor growth through modulating VEGF signaling pathway, which further validates its great potential in clinical practice.
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Registered trials
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