Plumbagin inhibits prostate cancer development in TRAMP mice via targeting PKCε, Stat3 and neuroendocrine markers
Menée sur un modèle murin d'adénocarcinome de la prostate, cette étude montre que la plumbagine, une substance extraite de la racine de la plante Plumbago zeylanica L, peut inhiber le développement des cellules tumorales en ciblant l'expression de la protéine kinase C epsilon, la phosphorylation du facteur de transcription STAT3 et des marqueurs neuro-endocriniens
Plumbagin (PL), 5-hydroxy-2methyl-4-napthoquinone, is a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L (also known as chitrak). PL has also been found in Juglans regia (English Walnut), Juglans cinerea (whitenut) and Juglans nigra (blacknut). The roots of Plumbago zeylanic have been used in Indian and Chinese systems of medicine for more than 2,500 years for the treatment of various types of ailments. We were the first to report that PL inhibits the growth and invasion of hormone refractory prostate cancer cells (Cancer Res. 68: 9024-9032, 2008). Now, we present that PL inhibits in vivo prostate cancer development in the transgenic adenocarcinoma of mouse prostate (TRAMP). PL-treatment (2mg/kg body weight i.p in 0.2 ml PBS, five days a week) to FVB-TRAMP resulted in a significant (P<0.01) decrease in prostate tumor size and urogenital apparatus weights at 13 and 20 weeks. Histopathological analysis revealed that PL-treatment inhibited progression of prostatic intraepithelial neoplasia (PIN) to poorly differentiated carcinoma (PDC). No animal exhibited diffuse tumor formation in PL-treated group at 13 weeks, while as 75 % of the vehicle-treated mice elicited diffuse PIN and large PDC at this stage. At 20 weeks, 25% of the PL-treated animals demonstrated diffuse PIN and 75% developed small PDC, whereas 100 % of the vehicle-treated mice showed large PDC. PL-treatment inhibited expression of PKCε, Stat3 phosphorylation, PCNA and neuroendocrine markers (synaptophysin and chromogranin-A) in excised prostate tumor tissues. Taken together, these results further suggest PL could be a novel chemopreventive agent against PCa.
http://carcin.oxfordjournals.org/content/early/2012/09/13/carcin.bgs291.abstract