ArticlePloS one2012
Combination therapy with gossypol reveals synergism against gemcitabine resistance in cancer cells with high BCL-2 expression.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- A case report of acute interstitial nephritis caused by cotton phenol.BMC urology · 2025Article
- A natural compound-empowered podophyllotoxin prodrug nanoassembly magnifies efficacy-toxicity benefits in cancer chemotherapy.Asian journal of pharmaceutical sciences · 2024Article
- Clinical trials of R-(-)-gossypol (AT-101) in newly diagnosed and recurrent glioblastoma: NABTT 0602 and NABTT 0702.PloS one · 2024Article
- Review
- Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.Pharmaceutics · 2022Review
- 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
- Prediction and identification of synergistic compound combinations against pancreatic cancer cells.iScience · 2021Article
- Involvement of Non-Coding RNAs in Chemo- and Radioresistance of Nasopharyngeal Carcinoma.Cancer management and research · 2021Review
- Oridonin overcomes the gemcitabine resistant PANC-1/Gem cells by regulating GST pi and LRP/1 ERK/JNK signalling.OncoTargets and therapy · 2019Article
- The emerging role of long non-coding RNAs in the drug resistance of colorectal cancer.International journal of clinical and experimental pathology · 2018Review
- The aldehyde group of gossypol induces mitochondrial apoptosis via ROS-SIRT1-p53-PUMA pathway in male germline stem cell.Oncotarget · 2017Article
- Long non-coding RNAs in anti-cancer drug resistance.Oncotarget · 2017Review
- Curcumin reduces mitomycin C resistance in breast cancer stem cells by regulating Bcl-2 family-mediated apoptosis.Cancer cell international · 2017Article
- The BH3-mimetic gossypol and noncytotoxic doses of valproic acid induce apoptosis by suppressing cyclin-A2/Akt/FOXO3a signaling.Oncotarget · 2015Article
- Article
- Small-molecule BH3 mimetic and pan-Bcl-2 inhibitor AT-101 enhances the antitumor efficacy of cisplatin through inhibition of APE1 repair and redox activity in non-small-cell lung cancer.Drug design, development and therapy · 2015Article
- A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors.Investigational new drugs · 2014Article
- MicroRNA profile in very young women with breast cancer.BMC cancer · 2014Article
- Gossypol toxicity from cottonseed products.TheScientificWorldJournal · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although gemcitabine is highly active in several cancer types, intrinsic and acquired drug resistance remains a major challenge. Overexpression of Bcl-2 has been associated with gemcitabine resistance. The aim of this study is to determine whether gossypol can overcome gemcitabine resistance in cell lines with high level of Bcl-2 expression in combination drug therapy. Our study demonstrated that in 10 cell lines derived from different cancers, high Bcl-2 baseline expression was observed in cell lines that were resistant to gemcitabine (GEM-R). Furthermore, synergistic effect of combination therapy was observed in gemcitabine-resistant (GEM-R) cell lines with high Bcl-2 expression, but not in a gemcitabine-sensitive (GEM-S) cell lines regardless of Bcl-2 expression. Gossypol treatment resulted in the decrease of anti-apoptotic genes such as Bcl-2 and Bcl-xl and an upregulation of the pro-apoptotic gene, Noxa. Furthermore, the addition of gossypol to gemcitabine resulted in lower expressions of anti-apoptotic genes compared to gemcitabine alone. Gene expression profiling in GEM-R and GEM-S cell lines suggest that anti-apoptotic genes such as pAkt and PI3KR2 may play important role in gemcitabine resistance, while pro-apoptotic Bcl-2 related genes (Bad, Caspase-6 and Calpain-1) may regulate synergistic interaction in combination therapy.
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