Ye Fei, Jiang Shiquan, Volshonok Helen, Wu Josephine, Zhang David Y
Department of Pathology, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
Nutr Cancer. 2007;57(1):100-10. doi: 10.1080/01635580701268352.
Scutellaria baicalensis is a widely used Chinese herbal medicine historically used in antiinflammatory and anticancer therapy. The goals of the study were to 1) determine its in vitro and in vivo anti-prostate cancer activity, 2) investigate its molecular mechanism directed at cell proliferation control including cyclooxygenase-2(COX-2) prostaglandin E2 (PGE2) and cyclins/cdks pathways, and 3) compare it with those of PC-SPES (PC stands for prostate cancer and spes is Latin for hope), a former herbal mixture for prostate cancer treatment of which S. baicalensis is a major constituent. Two human prostate cancer cell lines (LNCaP, androgen dependent, and PC-3, androgen independent) were assessed for growth inhibition. S. baicalensis exerted dose- and time-dependent increased growth inhibition in both cell lines. However, the PC-3 cells IC50 (50% growth inhibition concentration) were slightly more sensitive than LNCaP cells (IC50=0.15 mg/ml), although the former is androgen independent. S. baicalensis was more effective in inhibition of cell growth compared with PC-SPES (IC50=0.38 mg/ml for PC-3 cells). Significant reduction of PGE2 synthesis in both cells after treatment with S. baicalensis resulted from direct inhibition of COX-2 activity rather than COX-2 protein suppression. S. baicalensis also inhibited prostate-specific antigen production in LNCaP cells. Finally, S. baicalensis suppressed expression of cyclin D1 in LNCaP cells, resulting in a G1 phase arrest, while inhibiting cdk1 expression and kinase activity in PC-3 cells, ultimately leading to a G2/M cell cycle arrest. Animal studies showed a 50% reduction in tumor volume after a 7-wk treatment period. This study demonstrated that S. baicalensis may be a novel anticancer agent for the treatment of prostate cancer.
黄芩是一种广泛应用的中草药，历史上用于抗炎和抗癌治疗。本研究的目的是：1）确定其体外和体内抗前列腺癌活性；2）研究其针对细胞增殖控制的分子机制，包括环氧合酶-2（COX-2）、前列腺素E2（PGE2）和细胞周期蛋白/细胞周期蛋白依赖性激酶（cdks）途径；3）将其与PC-SPES（PC代表前列腺癌，spes在拉丁语中意为希望）进行比较，PC-SPES是一种以前用于治疗前列腺癌的草药混合物，黄芩是其主要成分。评估了两种人前列腺癌细胞系（LNCaP，雄激素依赖性；PC-3，雄激素非依赖性）的生长抑制情况。黄芩在两种细胞系中均呈现出剂量和时间依赖性的生长抑制增强。然而，PC-3细胞的半数抑制浓度（IC50）比LNCaP细胞略敏感（IC50 = 0.15 mg/ml），尽管前者是雄激素非依赖性的。与PC-SPES相比（PC-3细胞的IC50 = 0.38 mg/ml），黄芩在抑制细胞生长方面更有效。用黄芩处理后，两种细胞中PGE2合成的显著减少是由于直接抑制COX-2活性而非抑制COX-2蛋白所致。黄芩还抑制LNCaP细胞中前列腺特异性抗原的产生。最后，黄芩抑制LNCaP细胞中细胞周期蛋白D1的表达，导致G1期阻滞，同时抑制PC-3细胞中cdk1的表达和激酶活性，最终导致G2/M期细胞周期阻滞。动物研究表明，经过7周的治疗期后，肿瘤体积减少了50%。本研究表明，黄芩可能是一种治疗前列腺癌的新型抗癌药物。
