Ikezoe Takayuki, Chen Sophie S, Tong Xian-Jun, Heber David, Taguchi Hirokuni, Koeffler H Phillip
Department of Internal Medicine, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Int J Oncol. 2003 Oct;23(4):1187-93.
PC-SPES is an eight herbal mixture that was shown to have activity against prostate cancer. Recently, we purified oridonin from Rabdosia rubescens, one component of PC-SPES, by high performance liquid chromatography (HPLC). The ability of oridonin to inhibit the proliferation of cancer cells was examined by MTT assay. Oridonin effectively inhibited the proliferation of a wide variety of cancer cells including those from prostate (LNCaP, DU145, PC3), breast (MCF-7, MDA-MB231), non-small cell lung (NSCL) (NCI-H520, NCI-H460, NCI-H1299) cancers, acute promyelocytic leukemia (NB4), and glioblastoma multiforme (U118, U138) with ED50s ranging from 1.8 to 7.5 micro g/ml. TUNEL assay and cell cycle analysis showed that oridonin induced apoptosis and G0/G1 cell cycle arrest in LNCaP prostate cancer cells. In addition, expression of p21waf1 was induced in LNCaP and NCI-H520 cells in a p53-dependent manner. Interestingly, when p53 was suppressed by over-expression of E6 from human papilloma virus type 16 (HPV-16), these cells lost their sensitivity to oridonin-induced growth inhibition and apoptosis. Taken together, oridonin inhibited the proliferation of cancer cells via apoptosis and cell cycle arrest with p53 playing a central role in several cancer types which express the wild-type p53 gene. Oridonin may be a novel, adjunctive therapy for a large variety of malignancies and probably represents one of the major, active components of PC-SPES.
PC-SPES是一种由八种草药组成的混合物，已被证明对前列腺癌具有活性。最近，我们通过高效液相色谱法（HPLC）从PC-SPES的一种成分冬凌草中纯化出冬凌草甲素。采用MTT法检测冬凌草甲素抑制癌细胞增殖的能力。冬凌草甲素能有效抑制多种癌细胞的增殖，包括前列腺癌（LNCaP、DU145、PC3）、乳腺癌（MCF-7、MDA-MB231）、非小细胞肺癌（NSCL）（NCI-H520、NCI-H460、NCI-H1299）、急性早幼粒细胞白血病（NB4）和多形性胶质母细胞瘤（U118、U138），半数有效剂量（ED50）范围为1.8至7.5微克/毫升。TUNEL检测和细胞周期分析表明，冬凌草甲素可诱导LNCaP前列腺癌细胞凋亡并使其停滞于G0/G1期细胞周期。此外，p21waf1在LNCaP和NCI-H520细胞中以p53依赖的方式被诱导表达。有趣的是，当人乳头瘤病毒16型（HPV-16）的E6蛋白过度表达抑制p53时，这些细胞对冬凌草甲素诱导的生长抑制和凋亡失去敏感性。综上所述，冬凌草甲素通过凋亡和细胞周期停滞抑制癌细胞增殖，p53在几种表达野生型p53基因的癌症类型中起核心作用。冬凌草甲素可能是一种针对多种恶性肿瘤的新型辅助治疗药物，可能是PC-SPES的主要活性成分之一。
