Nanoparticles with curcumin and piperine modulate steroid biosynthesis in prostate cancer

Sci Rep. 2025 Apr 19;15(1):13613. doi: 10.1038/s41598-025-98102-z.

Abstract

Endogenous androgens are pivotal in the development and progression of prostate cancer (PC). We investigated nanoparticle formulations of curcumin and piperine in modulating steroidogenesis within PC cells. Using multiple PC cell lines (LNCaP, VCaP, DU145 and PC3) we studied the effects of curcumin, piperine, and their nanoparticle formulations-curcumin nanoparticles, piperine nanoparticles, and curcumin-piperine nanoparticles (CPN)-on cell viability, migration, and steroid biosynthesis. Curcumin and its nanoparticle formulations significantly reduced cell viability in PC cells, with curcumin-piperine nanoparticles showing the highest efficacy. These treatments also inhibited cell migration, with CPN exhibiting the most pronounced effect. In assays for steroid biosynthesis, curcumin, and its nanoparticle formulations, as well as piperine and its nanoparticles, selectively inhibited 17α-hydroxylase and 17,20-lyase activities of cytochrome P450 17A1 (CYP17A1). Abiraterone, a CYP17A1 inhibitor, displayed a broader inhibition of steroid metabolism including cytochrome P450 21-hydroxylase activity, whereas curcumin and piperine provided a more targeted inhibition profile. Analysis of steroid metabolites by liquid chromatography-mass spectrometry revealed that CPN caused significant reduction of androstenedione and cortisol, suggesting potential synergistic effects. In conclusion, nanoformulations co-loaded with curcumin and piperine offer an effective approach to targeting steroidogenesis and could be promising candidates for therapies aimed at managing androgen-dependent PC.

Keywords: Androgen synthesis; CYP17A1; Curcumin nanoparticles; Nanoparticle formulations; Prostate cancer; Steroidogenesis.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism
  • Caco-2 Cells
  • Cell Cycle / drug effects
  • Curcuma
  • Curcumin* / chemistry
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Cytochrome P-450 Enzyme Inhibitors* / pharmacology
  • Cytochrome P-450 Enzyme Inhibitors* / therapeutic use
  • Drug Screening Assays, Antitumor
  • Gene Expression / drug effects
  • Humans
  • Nanoparticle Drug Delivery System*
  • Nanoparticles / chemistry
  • PC-3 Cells
  • Phytochemicals / pharmacology
  • Phytochemicals / therapeutic use
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Prostatic Neoplasms* / drug therapy
  • Steroid 17-alpha-Hydroxylase* / antagonists & inhibitors
  • Steroids / metabolism
  • Wound Healing / drug effects

Substances

  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • Curcumin
  • piperine
  • Cytochrome P-450 Enzyme Inhibitors
  • Nanoparticle Drug Delivery System
  • Phytochemicals
  • Plant Extracts
  • Steroids
  • CYB5A protein, human