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.

BMC Cancer
|October 9, 2023
PubMed
Abstract

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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