Poncirus trifoliata (L.) Raf. Seed Extract Induces Cell Cycle Arrest and Apoptosis in the Androgen Receptor Positive LNCaP Prostate Cancer Cells

Int J Mol Sci. 2023 Nov 15;24(22):16351. doi: 10.3390/ijms242216351.

Abstract

Prostate cancer (PCa) is the second most common male cancer. Its incidence derives from the interaction between modifiable and non-modifiable factors. The progression of prostate cancer into a more aggressive phenotype is associated with chronic inflammation and increased ROS production. For their biological properties, some phytochemicals from fruits and vegetable emerge as a promise strategy for cancer progression delay. These bioactive compounds are found in the highest amounts in peels and seeds. Poncirus trifoliata (L.) Raf. (PT) has been widely used in traditional medicine and retains anti-inflammatory, anti-bacterial, and anticancer effects. The seeds of P. trifoliata were exhaustively extracted by maceration with methanol as the solvent. The cell proliferation rate was performed by MTT and flow cytometry, while the apoptosis signals were analyzed by Western blotting and TUNEL assay. P. trifoliata seed extract reduced LNCaP and PC3 cell viability and induced cell cycle arrest at the G0/G1phase and apoptosis. In addition, a reduction in the AKT/mTOR pathway has been observed together with the up-regulation of stress-activated MAPK (p38 and c-Jun N-terminal kinase). Based on the study, the anti-growth effects of PT seed extract on prostate tumor cells give indications on the potential of the phytochemical drug for the treatment of this type of cancer. However, future in-depth studies are necessary to identify which components are mainly responsible for the anti-neoplastic response.

Keywords: AKT/mTOR pathway; LNCaP; MAPKs; Poncirus trifoliata seed extract; apoptosis.

MeSH terms

  • Apoptosis
  • Cell Cycle
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Male
  • Plant Extracts / pharmacology
  • Poncirus* / chemistry
  • Prostatic Neoplasms* / metabolism
  • Receptors, Androgen
  • Seeds / metabolism

Substances

  • Receptors, Androgen
  • Plant Extracts

Grants and funding

This research was funded by a special award to the Department of Pharmacy, Health and Nutritional Sciences of the University of Calabria (Italy) PON ARS01_00568 “SI.F.I.PA.CRO.DE.—Sviluppo e industrializzazione farmaci innovativi per terapia molecolare personalizzata PA.CRO.DE. (B29C20000360005)” and by the MIUR ex 60% to F.G.