Naringenin protects HaCaT human keratinocytes against UVB-induced apoptosis and enhances the removal of cyclobutane pyrimidine dimers from the genome.
Many naturally occurring agents are believed to protect against UV-induced skin damage. In this study, we have investigated the effects of naringenin (NG), a naturally occurring citrus flavonone, on the removal of UVB-induced cyclobutane pyrimidine dimers (CPD) from the genome and apoptosis in immortalized p53-mutant human keratinocyte HaCaT cells. The colony-forming assay shows that treatment with NG significantly increases long-term cell survival after UVB irradiation. NG treatment also protects the cells from UVB-induced apoptosis, as indicated by the absence of the 180 base pair DNA ladders and the appearance of sub-G1 peak using agarose gel electrophoresis and flow cytometric analysis, respectively. The UVB-induced poly (ADP-ribose) polymerase-1 (PARP-1) cleavage, caspase activation and Bax/Bcl2 ratio were modulated following NG treatment, indicating an antiapoptotic effect of NG in UVB-damaged cells that occurs at least in part via caspase cascade pathway. Moreover, treatment of UVB-irradiated HaCaT cells with NG enhances the removal of CPD from the genome, as observed by both direct quantitation of CPD in genomic DNA and immuno-localization of the damage within the nuclei. The study provides a molecular basis for the action of NG as a promising natural flavonoid in preventing skin aging and carcinogenesis.
El-Mahdy
Mohamed A
MA
Department of Radiology, The Ohio State University, Columbus, OH, USA.
Zhu
Qianzheng
Q
Wang
Qi-En
QE
Wani
Gulzar
G
Patnaik
Srinivas
S
Zhao
Qun
Q
Arafa
El-Shaimaa
el-S
Barakat
Bassant
B
Mir
Safita N
SN
Wani
Altaf A
AA
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002460:Cell Line; D044950:Flavanones / Q000494:pharmacology*; D015894:Genome, Human; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects; D008969:Molecular Sequence Data; D011740:Pyrimidine Dimers / Q000302:isolation & purification*; D014466:Ultraviolet Rays
D044950:Flavanones; D011740:Pyrimidine Dimers; C005273:naringenin