Effects of Red Sorghum-Derived Deoxyanthocyanidins and Their O-β-D-Glucosides on E-Cadherin Promoter Activity in PC-3 Prostate Cancer Cells

Molecules. 2024 Apr 21;29(8):1891. doi: 10.3390/molecules29081891.

Abstract

Although much less common than anthocyanins, 3-Deoxyanthocyanidins (3-DAs) and their glucosides can be found in cereals such as red sorghum. It is speculated that their bioavailability is higher than that of anthocyanins. Thus far, little is known regarding the therapeutic effects of 3-DAs and their O-β-D-glucosides on cancer, including prostate cancer. Thus, we evaluated their potential to decrease cell viability, to modulate the activity of transcription factors such as NFκB, CREB, and SOX, and to regulate the expression of the gene CDH1, encoding E-Cadherin. We found that 4',7-dihydroxyflavylium chloride (P7) and the natural apigeninidin can reduce cell viability, whereas 4',7-dihydroxyflavylium chloride (P7) and 4'-hydroxy-7-O-β-D-glucopyranosyloxyflavylium chloride (P3) increase the activities of NFkB, CREB, and SOX transcription factors, leading to the upregulation of CDH1 promoter activity in PC-3 prostate cancer cells. Thus, these compounds may contribute to the inhibition of the epithelial-to-mesenchymal transition in cancer cells and prevent the metastatic activity of more aggressive forms of androgen-resistant prostate cancer.

Keywords: 3-deoxyanthocyanidin; 3-deoxyanthocyanin; E-cadherin; PC-3 cells; transcription factors.

MeSH terms

  • Anthocyanins* / chemistry
  • Anthocyanins* / pharmacology
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cadherins* / genetics
  • Cadherins* / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucosides* / chemistry
  • Glucosides* / pharmacology
  • Humans
  • Male
  • NF-kappa B / metabolism
  • PC-3 Cells
  • Promoter Regions, Genetic*
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Sorghum* / chemistry

Substances

  • Cadherins
  • Anthocyanins
  • Glucosides
  • CDH1 protein, human
  • Antigens, CD
  • NF-kappa B