ArticleMolecular medicine (Cambridge, Mass.)2011
The p53 upregulated modulator of apoptosis (PUMA) chemosensitizes intrinsically resistant ovarian cancer cells to cisplatin by lowering the threshold set by Bcl-x(L) and Mcl-1.
Article in Molecular medicine (Cambridge, Mass.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- Unlocking the mitochondrial functional code: unraveling the pathogenesis of ovarian cancer and innovative targets to inhibit malignant behavior.Journal of translational medicine · 2025Review
- PUMA mediated afatinib-induced apoptosis in glioma cells.Archives of medical science : AMS · 2025Article
- Mechanisms of the JNK/p38 MAPK signaling pathway in drug resistance in ovarian cancer.Frontiers in oncology · 2025Review
- Mapping the Anti-Cancer Activity of α-Connexin Carboxyl-Terminal (aCT1) Peptide in Resistant HER2+ Breast Cancer.Cancers · 2024Article
- New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions.Cancer metastasis reviews · 2023Review
- IDO1 Modulates the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin through ROS/p53-Dependent Apoptosis.International journal of molecular sciences · 2022Article
- Effects of trans-(±)-kusunokinin on chemosensitive and chemoresistant ovarian cancer cells.Oncology letters · 2022Article
- MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells.Journal of ovarian research · 2021Review
- Platinum drugs and taxanes: can we overcome resistance?Cell death discovery · 2021Review
- The therapeutic potential of attenuated diphtheria toxin delivered by an adenovirus vector with survivin promoter on human lung cancer cells.Cancer biology & therapy · 2021Article
- Inferring Differential Networks by Integrating Gene Expression Data With Additional Knowledge.Frontiers in genetics · 2021Article
- Bcl‑2 family: Novel insight into individualized therapy for ovarian cancer (Review).International journal of molecular medicine · 2020Review
- Apigenin induces apoptosis and counteracts cisplatin-induced chemoresistance via Mcl-1 in ovarian cancer cells.Experimental and therapeutic medicine · 2020Article
- Intramuscular accumulation of pentadecanoic acid activates AKT1 to phosphorylate NCOR1 and triggers FOXM1-mediated apoptosis in the pathogenesis of sarcopenia.American journal of translational research · 2020Article
- Ipatasertib, a novel Akt inhibitor, induces transcription factor FoxO3a and NF-κB directly regulates PUMA-dependent apoptosis.Cell death & disease · 2018Article
- Hesperidin inhibits ovarian cancer cell viability through endoplasmic reticulum stress signaling pathways.Oncology letters · 2017Article
- The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of ovarian cancer cells.Oncotarget · 2017Article
- Pazopanib, a novel multi-kinase inhibitor, shows potent antitumor activity in colon cancer through PUMA-mediated apoptosis.Oncotarget · 2017Article
- Changes in the in vitro activity of platinum drugs when administered in two aliquots.BMC cancer · 2016Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer is the number one cause of death from gynecologic malignancy. A defective p53 pathway is a hallmark of ovarian carcinoma. The p53 mutation correlates significantly with resistance to platinum-based chemotherapy, early relapse and shortened overall survival in ovarian cancer patients. PUMA (p53 upregulated modulator of apoptosis), a BH3-only Bcl-2 family protein, was recently identified as a transcriptional target of p53 and a potent apoptosis inducer in various cancer cells. In this study, we showed that the induction of PUMA by cisplatin was abolished in p53-deficient SKOV3 cells. Elevated expression of PUMA-induced apoptosis and sensitized A2780s and SKOV3 ovarian cancer cells to cisplatin, and the combination of PUMA and low-dose cisplatin, significantly suppressed xenograft tumor growth in vivo through enhanced induction of apoptosis compared with treatment with PUMA or cisplatin alone. The effects of PUMA were mediated by enhanced caspase activation and release of cytochrome c and Smac (second mitochondria-derived activator of caspase) into the cytosol. Furthermore, PUMA chemosensitized intrinsically resistant SKOV3 cells to cisplatin through downregulation of B-cell lymphoma-extra large (Bcl-x(L)) and myeloid cell leukemia sequence 1 (Mcl-1). PUMA-mediated Bcl-x(L) downregulation mainly happened at the transcription level, whereas PUMA-induced Mcl-1 down-regulation was associated with caspase-dependent cleavage and proteasome-mediated degradation. To our knowledge, these data suggest a new mechanism by which overexpression of PUMA enhances sensitivity of SKOV3 cells to cisplatin by lowering the threshold set simultaneously by Bcl-x(L) and Mcl-1. Taken together, our findings indicate that PUMA is an important modulator of therapeutic responses of ovarian cancer cells and is potentially useful as a chemosensitizer in ovarian cancer therapy.
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