title: Photo-excitation of carotenoids causes cytotoxicity via singlet oxygen production.
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.
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, Inage-ku, Chiba, Japan. yoshii@nirs.go.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshii
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yoshii
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Asai
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takaichi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujibayashi
mesh_terms: D002338:Carotenoids / Q000494:pharmacology* / Q000528:radiation effects / Q000627:therapeutic use; D003603:Cytotoxins / Q000494:pharmacology / Q000528:radiation effects / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000494:pharmacology* / Q000528:radiation effects / Q000627:therapeutic use; D004578:Electron Spin Resonance Spectroscopy; D006367:HeLa Cells; D006801:Humans; D008027:Light; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000528:radiation effects / Q000627:therapeutic use; D026082:Singlet Oxygen / Q000378:metabolism*; D012871:Skin Diseases / Q000188:drug therapy; D014216:Triacetoneamine-N-Oxyl / Q000031:analogs & derivatives / Q000737:chemistry; D024341:Xanthophylls / Q000494:pharmacology* / Q000528:radiation effects / Q000627:therapeutic use
chemical_list: D003603:Cytotoxins; D003879:Dermatologic Agents; D017319:Photosensitizing Agents; D024341:Xanthophylls; C025164:fucoxanthin; D026082:Singlet Oxygen; C003314:siphonaxanthin; D014216:Triacetoneamine-N-Oxyl; C002273:tempidon; D002338:Carotenoids; C011947:neoxanthin