Enhanced effects of citrate on UVB-induced apoptosis of B16 melanoma cells

Pharmazie. 2009 Dec;64(12):829-33.

Abstract

Ultraviolet (UV) radiation is a major risk factor for the development of melanoma. Recent studies have reported that the intake of citrate-containing juices may reduce the risk of cancer. Thus, we investigated the effects of citrate on UVB-irradiated B16 murine melanoma cells. B16 cells had more evident apoptotic features with the combination of citrate/UVB than by citrate or UVB alone; cell death of HaCaT human keratinocytes was not observed with citrate/UVB. Western blot analysis demonstrated that citrate/UVB led to phosphorylation of the stress signaling proteins, such as c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Furthermore, citrate/UVB caused activation of caspase-9/-3 as well as cleavage of poly(ADP-ribose) polymerase (PARP). Correspondingly, cell cycle analysis showed that citrate/UVB clearly increased the sub-G0/G1 phase, which indicated apoptotic cell death of B16 cells. Therefore, our study has demonstrated that sub-lethal doses of citrate enhanced the apoptotic cell death of melanoma cells under UVB irradiation. From these results, we suggest that citrate might reduce the risk of developing melanoma induced by UVB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Blotting, Western
  • Caspases / biosynthesis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Citrates / pharmacology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / biosynthesis
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / pathology*
  • Melanoma, Experimental / radiotherapy
  • Poly(ADP-ribose) Polymerases / biosynthesis
  • Radiation-Protective Agents*
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Ultraviolet Rays*
  • p38 Mitogen-Activated Protein Kinases / biosynthesis

Substances

  • Apoptosis Regulatory Proteins
  • Citrates
  • Radiation-Protective Agents
  • Poly(ADP-ribose) Polymerases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspases