Resveratrol-sensitized UVA induced apoptosis in human keratinocytes through mitochondrial oxidative stress and pore opening.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol compound, is derived from natural products such as the skin of red grapes, blueberries and cranberries. Resveratrol not only exhibits antioxidant, cardioprotection, and anti-aging properties, but can also inhibit cancer cell growth and induce apoptosis. It has been shown that resveratrol inhibits the activation of Nf-κB and subsequently down regulates the expression of Nf-κB regulated genes such as interleukin-2 and Bcl-2, leading to cell cycle arrest and increased apoptosis in multiple myeloma cells. In the skin, resveratrol has been reported to sensitize keratinocytes to UVA induced apoptosis. However, the effect of resveratrol on opening of the mitochondrial permeability transition pore has not been previously examined. Our data show that UVA (14 J/cm(2)) along with resveratrol causes massive oxidative stress in mitochondria. As a consequence of oxidative stress, the mitochondrial membrane potential decreases which results in opening of the mitochondrial pores ultimately leading to apoptosis in human keratinocytes. These results may have clinical implications for development of future chemotherapeutic treatment for tumors of the skin.
Southern Arizona VA Health Care System, Tucson, AZ 85724, USA.
Jean Z
JZ
Boyer
Jana
J
Jandova
Jaroslav
J
Janda
Frank R
FR
Vleugels
David A
DA
Elliott
James E
JE
Sligh
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects*; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000528:radiation effects*; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014466:Ultraviolet Rays
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013267:Stilbenes; D000077185:Resveratrol