The flavonoid luteolin increases the resistance of normal, but not malignant keratinocytes, against UVB-induced apoptosis.
Adequate protection of skin against the carcinogenic effects of UVB irradiation is essential. Flavonoids may have a conspicuous role in cancer prevention because of their antioxidant, anti-inflammatory, and growth-inhibitory effects. Therefore, we tested the effects of the flavone luteolin (LUT) on selected parameters of the sunburn response in normal human keratinocytes, exposed to physiological doses of UVB. LUT attenuated UVB-induced cell death through delay and inhibition of intrinsic apoptotic signaling. Moreover, LUT not only predominantly affected the mitochondrial apoptosis pathway through its antioxidant capacity, but also changed the balance of Bcl2 (B-cell leukemia/lymphoma 2)-family members. Furthermore, LUT had inhibitory effects on the UVB-induced release of the inflammatory mediators, IL-1alpha and prostaglandin-E(2). Using different cell lines derived from squamous cell carcinomas, we showed that LUT did not increase the resistance of malignant keratinocytes to UVB. Our data suggest that LUT inhibits different aspects of the sunburn response, which results ultimately in an increased survival of normal keratinocytes, whereas the sensitivity of malignant cells to UVB remain unchanged. Hence, LUT might have value in new photoprotective applications or improve existing ones.
Verschooten
Lien
L
Laboratory of Dermatology, Catholic University of Leuven, Leuven, Belgium.
Smaers
Katrien
K
Van Kelst
Sofie
S
Proby
Charlotte
C
Maes
Daniel
D
Declercq
Lieve
L
Agostinis
Patrizia
P
Garmyn
Marjan
M
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D019610:Cytoprotection; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D047311:Luteolin / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000473:pathology*; D013471:Sunburn / Q000188:drug therapy / Q000473:pathology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000975:Antioxidants; D047311:Luteolin