Journal Article

Plumbagin inhibits prostate cancer development in TRAMP mice via targeting PKCε, Stat3 and neuroendocrine markers

Bilal Bin Hafeez, Weixiong Zhong, Ala Mustafa, Joseph W. Fischer, Olya Witkowsky and Ajit K. Verma

in Carcinogenesis

Volume 33, issue 12, pages 2586-2592
Published in print December 2012 | ISSN: 0143-3334
Published online September 2012 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgs291
Plumbagin inhibits prostate cancer development in TRAMP mice via targeting PKCε, Stat3 and neuroendocrine markers

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Plumbagin (PL), 5-hydroxy-2-methyl-1,4-naphthoquinone, 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 P. zeylanica have been used in Indian and Chinese systems of medicine for more than 2500 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 (PCa) cells [Aziz,M.H. et al. (2008) Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer. Cancer Res., 68, 9024–9032.]. Now, we present that PL inhibits in vivo PCa development in the transgenic adenocarcinoma of mouse prostate (TRAMP). PL treatment (2mg/kg body weight i.p. in 0.2ml phosphate-buffered saline, 5 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, whereas 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 protein kinase C epsilon (PKCε), signal transducers and activators of transcription 3 phosphorylation, proliferating cell nuclear antigen 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.

Journal Article.  4869 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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