Photo-excitation of carotenoids causes cytotoxicity via singlet oxygen production

Biochem Biophys Res Commun. 2012 Jan 6;417(1):640-5. doi: 10.1016/j.bbrc.2011.12.024. Epub 2011 Dec 11.

Abstract

Carotenoids, natural pigments widely distributed in algae and plants, have a conjugated double bond system. Their excitation energies are correlated with conjugation length. We hypothesized that carotenoids whose energy states are above the singlet excited state of oxygen (singlet oxygen) would possess photosensitizing properties. Here, we demonstrated that human skin melanoma (A375) cells are damaged through the photo-excitation of several carotenoids (neoxanthin, fucoxanthin and siphonaxanthin). In contrast, photo-excitation of carotenoids that possess energy states below that of singlet oxygen, such as β-carotene, lutein, loroxanthin and violaxanthin, did not enhance cell death. Production of reactive oxygen species (ROS) by photo-excited fucoxanthin or neoxanthin was confirmed using a reporter assay for ROS production with HeLa Hyper cells, which express a fluorescent indicator protein for intracellular ROS. Fucoxanthin and neoxanthin also showed high cellular penetration and retention. Electron spin resonance spectra using 2,2,6,6-tetramethil-4-piperidone as a singlet oxygen trapping agent demonstrated that singlet oxygen was produced via energy transfer from photo-excited fucoxanthin to oxygen molecules. These results suggest that carotenoids such as fucoxanthin, which are capable of singlet oxygen production through photo-excitation and show good penetration and retention in target cells, are useful as photosensitizers in photodynamic therapy for skin disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carotenoids / pharmacology*
  • Carotenoids / radiation effects
  • Carotenoids / therapeutic use
  • Cytotoxins / pharmacology
  • Cytotoxins / radiation effects
  • Cytotoxins / therapeutic use
  • Dermatologic Agents / pharmacology*
  • Dermatologic Agents / radiation effects
  • Dermatologic Agents / therapeutic use
  • Electron Spin Resonance Spectroscopy
  • HeLa Cells
  • Humans
  • Light
  • Photochemotherapy / methods
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / radiation effects
  • Photosensitizing Agents / therapeutic use
  • Singlet Oxygen / metabolism*
  • Skin Diseases / drug therapy
  • Triacetoneamine-N-Oxyl / analogs & derivatives
  • Triacetoneamine-N-Oxyl / chemistry
  • Xanthophylls / pharmacology*
  • Xanthophylls / radiation effects
  • Xanthophylls / therapeutic use

Substances

  • Cytotoxins
  • Dermatologic Agents
  • Photosensitizing Agents
  • Xanthophylls
  • fucoxanthin
  • Singlet Oxygen
  • siphonaxanthin
  • Triacetoneamine-N-Oxyl
  • tempidon
  • Carotenoids
  • neoxanthin