The contradictory role of febuxostat in ABCG2 expression and potentiating hypericin-mediated photodynamic therapy in colorectal cancers

Photochem Photobiol Sci. 2024 Jun;23(6):1067-1075. doi: 10.1007/s43630-024-00575-w. Epub 2024 Apr 16.

Abstract

Photodynamic Therapy (PDT) is an emerging method to treat colorectal cancers (CRC). Hypericin (HYP) is an effective mediator of PDT and the ABCG2 inhibitor, Febuxostat (FBX) could augment PDT. HT29 and HEK293 cells showed light dependant cytotoxic response to PDT in both 2D and 3D cell models. FBX co-treatment was not found to improve PDT cytotoxicity. Next, ABCG2 protein expression was observed in HT29 but not in HEK293 cells. However, ABCG2 gene expression analysis did not support protein expression results as ABCG2 gene expression results were found to be higher in HEK293 cells. Although HYP treatment was found to significantly reduce ABCG2 gene expression levels in both cell lines, FBX treatment partially restored ABCG2 gene expression. Our findings indicate that FBX co-treatment may not be suitable for augmenting HYP-mediated PDT in CRC but could potentially be useful for other applications.

Keywords: ABCG2; Colorectal cancer; Febuxostat; Hypericin; Photodynamic therapy.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2* / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily G, Member 2* / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2* / metabolism
  • Anthracenes* / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Survival / drug effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Febuxostat* / pharmacology
  • Febuxostat* / therapeutic use
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • Neoplasm Proteins* / antagonists & inhibitors
  • Neoplasm Proteins* / metabolism
  • Perylene* / analogs & derivatives
  • Perylene* / pharmacology
  • Photochemotherapy*
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • hypericin
  • Anthracenes
  • Perylene
  • ABCG2 protein, human
  • Febuxostat
  • Neoplasm Proteins
  • Photosensitizing Agents
  • Antineoplastic Agents