Photodynamic Activation of a Novel Chlorophyll-Enriched Green Propolis Compound Triggers Apoptosis in Renal Cell Carcinoma

Int J Mol Sci. 2025 Jul 18;26(14):6897. doi: 10.3390/ijms26146897.

Abstract

Renal cell carcinoma (RCC) presents significant therapeutic challenges due to its resistance to conventional treatments. Natural compounds with photodynamic properties, such as chlorophyll derivatives, offer potential for novel interventions. This study investigates the apoptotic effects of a chlorophyll-enriched green propolis compound activated by daylight-mediated photodynamic therapy (PDT) on RCC cells. A novel compound formulated from standardized ethanol extracts of Taiwanese green propolis, wheatgrass, and mulberry leaves was characterized using high-performance liquid chromatography (HPLC). Human RCC 786-O cells were treated with varying concentrations of the compound, with or without daylight PDT (570 nm). Cell viability was assessed via MTT assay, and median effective concentrations (EC50) were calculated. HPLC analysis identified Artepillin C as the major constituent. The compound induced dose-dependent cytotoxicity, which was significantly enhanced by daylight PDT. EC50 values dropped from 3.027 µL (compound alone) to 1.728 µL (with PDT), indicating synergistic efficacy. Cell viability significantly decreased in PDT-treated cells compared to non-treated controls (p < 0.05) indicating apoptosis. Daylight-activated PDT significantly amplifies the anticancer efficacy of the compound against RCC cells. Preliminary data suggest the potential of chlorophyll-enriched green propolis photodynamic activation (GPDT) as a natural adjunctive strategy for RCC, warranting further in vivo investigation.

Keywords: GPDT; Taiwanese green propolis; apoptosis; chlorophyll derivatives; nutraceuticals; photodynamic therapy (PDT); renal cancer.

MeSH terms

  • Apoptosis* / drug effects
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorophyll* / chemistry
  • Chlorophyll* / pharmacology
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / metabolism
  • Kidney Neoplasms* / pathology
  • Photochemotherapy* / methods
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Propolis* / chemistry
  • Propolis* / pharmacology

Substances

  • Propolis
  • Chlorophyll
  • Photosensitizing Agents