Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-kappaB pathway in human epidermoid carcinoma A431 cells.
Resveratrol has been reported to suppress cancer progression in several in vivo and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer, is known to induce cell death in cancerous cells. Here, we investigated whether resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced cell death. We examined the combined effect of UVB (30 mJ/cm(2)) and resveratrol (60 microM) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or resveratrol can inhibit cell proliferation and induce apoptosis. However, the combination of resveratrol and UVB exposure was associated with increased proliferation inhibition of A431 cells compared with either agent alone. Furthermore, results showed that resveratrol and UVB treatment of A431 cells disrupted the nuclear factor-kappaB (NF-kappaB) pathway by blocking phosphorylation of serine 536 and inactivating NF-kappaB and subsequent degradation of IkappaBalpha, which regulates the expression of survivin. Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701 of the important transcription factor signal transducer activator of transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein LIMK1, which reduced the motility of A431 cells. In conclusion, our study demonstrates that the combination of resveratrol and UVB act synergistically against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic agent against skin carcinogenesis.
Roy
Preeti
P
Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226001, India.
Madan
Esha
E
Kalra
Neetu
N
Nigam
Nidhi
N
George
Jasmine
J
Ray
Ratan Singh
RS
Hans
Rajendra K
RK
Prasad
Sahdeo
S
Shukla
Yogeshwer
Y
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D054461:Lim Kinases / Q000037:antagonists & inhibitors; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077185:Resveratrol; D012878:Skin Neoplasms / Q000378:metabolism / Q000517:prevention & control; D013267:Stilbenes / Q000494:pharmacology*; D000077022:Survivin; D014466:Ultraviolet Rays
D000975:Antioxidants; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D011838:Radiation-Sensitizing Agents; D013267:Stilbenes; D000077022:Survivin; C515892:LIMK1 protein, human; D054461:Lim Kinases; D000077185:Resveratrol