ArticleBlood2008
Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The trial behind it
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Who cites it
45 citing papers in PubMed, 132 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
- Review
- A case report of acute interstitial nephritis caused by cotton phenol.BMC urology · 2025Article
- Bax- Bcl-xL interaction dynamics during the progression of cell cycle and cell death using FLIM-FRET.Cell stress · 2025Review
- Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway.Journal of microbiology and biotechnology · 2022Article
- Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Xanthohumol and Gossypol Are Promising Inhibitors againstVaccines · 2020Article
- Glycan Mimetics from Natural Products: New Therapeutic Opportunities for Neurodegenerative Disease.Molecules (Basel, Switzerland) · 2019Review
- Autophagy in Cancer Cell Death.Biology · 2019Review
- Effects of gossypol on apoptosis‑related gene expression in racially distinct triple‑negative breast cancer cells.Oncology reports · 2019Article
- The Development and Current Use of BCL-2 Inhibitors for the Treatment of Chronic Lymphocytic Leukemia.Current hematologic malignancy reports · 2017Review
- Autophagy in Cancer Therapy.Frontiers in oncology · 2017Review
- AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations.BMC cancer · 2016Article
- Selenoprotein R Protects Human Lens Epithelial Cells against D-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.International journal of molecular sciences · 2016Article
- Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation.Frontiers in pediatrics · 2016Review
- Broad targeting of resistance to apoptosis in cancer.Seminars in cancer biology · 2015Review
- The BH3-mimetic gossypol and noncytotoxic doses of valproic acid induce apoptosis by suppressing cyclin-A2/Akt/FOXO3a signaling.Oncotarget · 2015Article
- Cell death by autophagy: emerging molecular mechanisms and implications for cancer therapy.Oncogene · 2015Review
- Inhibitory activity of apogossypol in human prostate cancer in vitro and in vivo.Molecular medicine reports · 2015Article
- Regulation of Mcl-1 expression in context to bone marrow stromal microenvironment in chronic lymphocytic leukemia.Neoplasia (New York, N.Y.) · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Gossypol, a cottonseed extract derivative, acts as a BH3-mimetic, binding to the BH3 pocket of antiapoptotic proteins and displacing pro-death partners to induce apoptosis. However, knowledge on the molecular underpinnings of its downstream effects is limited. Since chronic lymphocytic leukemia (CLL) cells express high levels of antiapoptotic proteins that act as a survival mechanism for these replicationally quiescent lymphocytes, we investigated whether gossypol induces apoptosis in these cells and what mechanism underlies gossypol-mediated cytotoxicity. Gossypol induced cell death in a concentration- and time-dependent manner; 24-hour incubation with 30 microM gossypol resulted in 50% cell death (median; range, 10%-80%; n = 47) that was not abrogated by pan-specific caspase inhibitor. Starting at 4 hours, the mitochondrial outer membrane was significantly permeabilized (median, 77%; range, 54%-93%; n = 15). Mitochondrial outer membrane permeabiliztaion (MOMP) was concurrent with increased production of reactive oxygen species (ROS); however, antioxidants did not abrogate gossypol-induced cell death. Mitochondrial membrane permeabilization was also associated with loss of intracellular adenosine triphosphate (ATP), activation of BAX, and release of cytochrome c and apoptosis-inducing factor (AIF), which was translocated to the nucleus. Blocking AIF translocation resulted in a decreased apoptosis, suggesting that AIF contributes to gossypol-mediated cytotoxicity in CLL lymphocytes.
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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.