Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), isolated from Plumbago zeylanica, inhibits Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas
Menée sur un modèle murin, cette étude montre que la plumbagine, une naphtoquinone extraite de la racine de la plante "Plumbago zeylanica", inhibe le développement du carcinome épidermoïde induit par les ultraviolets
Plumbagin (PL) (5-hydroxy-2-methyl-1,4-napthoquinone), a medicinal plant–derived naphthoquinone, was isolated from the roots of the Plumbago zeylanica L. (also known as Chitrak). The roots of Plumbago zeylanica L. have been used in Indian medicine for more than 2,500 years as an anti-atherogenic, cardiotonic, hepatoprotective, and neuroprotective agent. We present here that topical application of non-toxic doses (100-500 nmoles) of PL to skin elicits dose-dependent inhibition of ultraviolet radiation (UVR)-induced development of squamous cell carcinomas (SCC). In this experiment, FVB/N mice were exposed to UVR (2 kJ/m2) three times weekly from a bank of six Kodacel-filtered FS40 sunlamps (approximately 60% UVB and 40% UVA). Carcinoma incidence in mice treated with vehicle, 100, 200 or 500 nmoles PL, at 44 weeks post UVR, were 86%, 80% (p=0.67), 53% (p=0.12) and 7% (p=0.0075), respectively. Both vehicle and PL treated mice gained weight and did not exhibit any signs of toxicity during the entire period of the experiment. Molecular mechanisms associated with inhibition of UVR-induced development of SCC involved induction of apoptosis and inhibition of cell proliferation. Specific findings are that PL treatment: 1) inhibited UVR-induced DNA-binding of AP-1, NF-κB, Stat3 transcription factors and Stat3-regulated molecules (cdc25A and Survivin), 2) inhibited protein levels of pERK1/2, PI3K85, pAKTSer473, Bcl2, BclxL, PCNA, and cell cycle inhibitory proteins p27 and p21, and 3) increased UVR-induced fas-associated death domain (FADD) expression, PARP cleavage, and Bax/Bcl2 ratio. Taken together, our findings suggest that PL may be a novel agent for the prevention of skin cancer.
http://carcin.oxfordjournals.org/content/early/2011/11/08/carcin.bgr249.abstract 2011