Ubiquitin-specific protease 2a stabilizes MDM4 and facilitates the p53-mediated intrinsic apoptotic pathway in glioblastoma

Background: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments. Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency) at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i) growth inhibition through trypan blue exclusion assay and microphotography, ii) classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii) activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients. Key words: topotecan; genistein; intrinsic apoptotic cell death

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Faculty Opinions recommendation of Synaptic defects in ataxia mice result from a mutation in Usp14, encoding a ubiquitin-specific protease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1009695.139557 ◽

2002 ◽

Author(s):

Louis Ptacek

Keyword(s):

Specific Protease ◽

Ubiquitin Specific Protease

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Faculty Opinions recommendation of A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717957380.793461863 ◽

2012 ◽

Author(s):

Pengbo Zhou ◽

Jeffrey Hannah

Keyword(s):

Multiple Myeloma ◽

Small Molecule ◽

Small Molecule Inhibitor ◽

Myeloma Cells ◽

Molecule Inhibitor ◽

Specific Protease ◽

Ubiquitin Specific Protease

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Faculty Opinions recommendation of Ubiquitin-specific protease 19 regulates the stability of the E3 ubiquitin ligase MARCH6.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718519896.793514105 ◽

2016 ◽

Author(s):

Simon Wing

Keyword(s):

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Specific Protease ◽

Ubiquitin Specific Protease ◽

The Stability

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USP48 Sustains Chemoresistance and Metastasis in Ovarian Cancer

Current Cancer Drug Targets ◽

10.2174/1568009620666200503045400 ◽

2020 ◽

Vol 20 (9) ◽

pp. 689-699

Author(s):

Xuemeng Lei ◽

Xukun Li ◽

Hongyan Chen ◽

Zhihua Liu

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Migration And Invasion ◽

Clinical Samples ◽

Deubiquitinating Enzymes ◽

Potential Therapeutic Target ◽

Kaplan Meier ◽

Specific Protease ◽

Ubiquitin Specific Protease

Background: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear. Objective: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation. Methods: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice. Results: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy. Conclusion: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.

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