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A Rapid Filter Insert-based 3D Culture System for Primary Prostate Cell Differentiation
Published on: February 13, 2017
Unveiling poly(rC)-binding protein 2 as the target protein for curcusone C against prostate cancer: mechanism
Lan Huang1, Buqing Ma1, Chong Zhang1
1School of medicine, Huaqiao University, Quanzhou, 362021, China.
Background:
Prostate cancer is a disease that seriously troubles men. However, there are some inevitable limitations in interventional therapy for prostate cancer patients at present, most of which are caused by low selectivity and high toxic side effects due to unclear drug targets. In this study, we identified the target protein of Curcusone C with anti-prostate cancer potential activity and verified its target and mechanism of action.
Methods:
Click chemistry-activity based proteomics profiling (CC-ABPP) method was used to find target protein of Curcusone C against prostate cancer. Competitive CC-ABPP, drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) methods were used to verifying the target protein. Moreover, potential mechanism was validated by western blot in vitro and by hematoxylin-eosin (HE) staining, detection of apoptosis in tumor tissue (TUNEL), and immunohistochemical (IHC) in vivo.
Results:
We found that poly(rC)-binding protein 2 (PCBP2) was the target protein of Curcusone C. In addition, Curcusone C might disrupt the Bax/Bcl-2 balance in PC-3 cells by inhibiting the expression of the target protein PCBP2, thereby inducing mitochondrial damage and activation of the mitochondrial apoptosis pathway, and ultimately inducing apoptosis of prostate cancer cells.
Conclusions:
Curcusone C is a potential compound with anti-prostate cancer activity, and this effect occurs by targeting the PCBP2 protein, which in turn may affect the TGF/Smad signaling pathway and Bax/Bcl-2 balance. Our results laid a material and theoretical foundation for Curcusone C, to be widely used in anti-prostate cancer.
Insights
Curcusone C targets poly(rC)-binding protein 2 (PCBP2) to induce prostate cancer cell apoptosis. This compound may offer a new therapeutic strategy by disrupting the Bax/Bcl-2 balance and mitochondrial pathways.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Prostate cancer presents significant therapeutic challenges due to limitations in current treatments, including low selectivity and high toxicity.
- Unclear drug targets contribute to the ineffectiveness and adverse effects of existing prostate cancer therapies.
Purpose of the Study:
- To identify the specific protein target of Curcusone C, a compound with potential anti-prostate cancer activity.
- To elucidate the mechanism of action by which Curcusone C exerts its anti-cancer effects.
Main Methods:
- Click chemistry-activity based proteomics profiling (CC-ABPP) was employed to identify the target protein.
- Target validation was performed using competitive CC-ABPP, drug affinity responsive target stability (DARTS), and surface plasmon resonance (SPR).
- Mechanism of action was assessed through in vitro western blot and in vivo studies including HE staining, TUNEL assay, and IHC.
Main Results:
- Poly(rC)-binding protein 2 (PCBP2) was identified as the direct target protein of Curcusone C.
- Curcusone C inhibits PCBP2 expression, leading to disruption of the Bax/Bcl-2 balance in PC-3 cells.
- This inhibition induces mitochondrial damage, activates the mitochondrial apoptosis pathway, and promotes prostate cancer cell death.
Conclusions:
- Curcusone C demonstrates potential as an anti-prostate cancer agent by targeting PCBP2.
- The compound's mechanism involves modulating the Bax/Bcl-2 balance and potentially affecting the TGF/Smad signaling pathway.
- These findings provide a foundation for the clinical development of Curcusone C for prostate cancer treatment.
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