Department of Human Oncology, Wisconsin Institute of Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA.
Carcinogenesis. 2012 Dec;33(12):2586-92. doi: 10.1093/carcin/bgs291. Epub 2012 Sep 13.
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 (2 mg/kg body weight i.p. in 0.2 ml 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.
白花丹素（PL），5-羟基-2-甲基-1,4-萘醌，是一种醌类成分，从药用植物白花丹（也称为 chitrak）的根中分离得到。PL 也存在于核桃 Juglans regia（英语核桃）、核桃 Juglans cinerea（白胡桃）和黑胡桃 Juglans nigra 中。P.zeylanica 的根在印度和中国的医学系统中已经使用了超过 2500 年，用于治疗各种类型的疾病。我们是第一个报道 PL 抑制激素难治性前列腺癌（PCa）细胞生长和侵袭的人[Aziz，MH 等人。（2008 年）植物来源的萘醌白花丹素是激素难治性前列腺癌生长和侵袭的新型抑制剂。癌症 Res.，68，9024-9032。]。现在，我们提出 PL 抑制转基因腺癌小鼠前列腺（TRAMP）中的体内 PCa 发展。PL 治疗（2mg/kg 体重腹腔注射 0.2ml 磷酸盐缓冲液，每周 5 天）对 FVB-TRAMP 的结果是前列腺肿瘤大小和泌尿生殖器官重量显著（P<0.01）下降，分别在 13 周和 20 周。组织病理学分析显示 PL 治疗抑制前列腺上皮内瘤变（PIN）向低分化癌（PDC）的进展。在 13 周时，PL 治疗组没有动物表现出弥漫性肿瘤形成，而在对照组中，75%的小鼠在这个阶段表现出弥漫性 PIN 和大 PDC。在 20 周时，25%的 PL 治疗动物表现出弥漫性 PIN，75%发展为小 PDC，而 100%的对照组小鼠表现出大 PDC。PL 治疗抑制了前列腺肿瘤组织中蛋白激酶 C ɛ（PKCε）、信号转导和转录激活因子 3 磷酸化、增殖细胞核抗原和神经内分泌标志物（突触素和嗜铬粒蛋白-A）的表达。综上所述，这些结果进一步表明 PL 可能是一种新型的针对 PCa 的化学预防剂。
