Evaluation of the effect of 5-aminolevulinic acid hexyl ester (H-ALA) PDT on EBV LMP1 protein expression in human nasopharyngeal cells

Photodiagnosis Photodyn Ther. 2020 Jun:30:101801. doi: 10.1016/j.pdpdt.2020.101801. Epub 2020 Apr 30.

Abstract

Nasopharyngeal carcinoma (NPC) is of high prevalence in Hong Kong and southern China. The pathogenesis of NPC is closely associated with Epstein-Barr virus (EBV) infection via regulation of viral oncoprotein latent membrane protein 1 (LMP1). The conventional treatment for NPC is chemo-radiotherapy, but the prognosis remains poor for advanced stage, recurrent and metastatic NPC. Photodynamic therapy (PDT) is a therapeutic approach to combat tumors. PDT effectiveness depends on the interaction of photosensitizers, light and molecular oxygen. 5- aminolevulinic acid hexyl derivative (H-ALA) is one of the photosensitizers derived from 5-ALA. H-ALA with improved lipophilic properties by adding a long lipophilic chain (hexyl group) to 5-ALA, resulted in better penetration into cell cytoplasm. In this study, the effect of H-ALA-PDT on NPC cells (EBV positive C666-1 and EBV negative CNE2) was investigated. The H-ALA mediated cellular uptake and cytotoxicity was revealed via flow cytometry analysis and MTT assay respectively. H-ALA PDT mediated protein modulation was analysed by western blot analysis. Our finding reported that the cellular uptake of H-ALA in C666-1 and CNE2 cells was in a time dependent manner. H-ALA PDT was effective to C666-1 and CNE2 cells. EBV LMP1 proteins was expressed in C666-1 cells only and its expression was responsive to H-ALA PDT in a dose dependent manner. This work revealed the potential of H-ALA PDT as a treatment regiment for EBV positive NPC cells. Understanding the mechanism of H-ALA mediated PDT could develop improved strategies for the treatment of NPC.

Keywords: EBV; H-ALA; LMP1 protein; PDT.

MeSH terms

  • Aminolevulinic Acid / analogs & derivatives*
  • Aminolevulinic Acid / pharmacokinetics
  • Aminolevulinic Acid / pharmacology
  • Cell Line, Tumor
  • Cell Survival
  • Herpesvirus 4, Human / drug effects
  • Humans
  • Lasers, Semiconductor / therapeutic use
  • Low-Level Light Therapy / methods*
  • Nasopharyngeal Neoplasms / drug therapy*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacokinetics
  • Photosensitizing Agents / pharmacology*
  • Protoporphyrins / pharmacokinetics
  • Viral Matrix Proteins / drug effects*

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • Photosensitizing Agents
  • Protoporphyrins
  • Viral Matrix Proteins
  • Aminolevulinic Acid
  • protoporphyrin IX
  • 5-aminolevulinic acid hexyl ester