Wang Wei, Rayburn Elizabeth R, Hao Miao, Zhao Yuqing, Hill Donald L, Zhang Ruiwen, Wang Hui
Department of Pharmacology and Toxicology and Division of Clinical Pharmacology, and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Prostate. 2008 Jun 1;68(8):809-19. doi: 10.1002/pros.20742.
Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro.
We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds.
25-OH-PPD, but not 25-OH-PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation therapy to improve the anti-tumor effects. Further, in both PC3 and LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated low toxicity to non-cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies.
The newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate cancer therapeutic agent.
人参及其成分具有多种生物学效应，包括抗氧化、抗癌、抗诱变和抗肿瘤活性，近期研究聚焦于其在人类癌症预防和治疗中的价值。我们最近从人参中分离出25-羟基原人参二醇（25-OH-PPD）和25-羟基原人参三醇（25-OH-PPT），并评估了它们的体外抗癌活性。
我们比较了这两种化合物对人前列腺癌LNCaP和PC3细胞的体外作用以及在小鼠PC3异种移植肿瘤模型中的作用。我们还初步确定了这些化合物的作用机制。
25-OH-PPD可抑制前列腺癌细胞生长和增殖，诱导细胞凋亡，并导致细胞周期停滞于G1期，而25-OH-PPT则无此作用。在携带PC3异种移植肿瘤的裸鼠中，25-OH-PPD以剂量依赖性方式抑制肿瘤生长，并且可以安全地与化疗药物（多西他赛和吉西他滨）及放射治疗联合使用以提高抗肿瘤效果。此外，在PC3和LNCaP细胞系中，25-OH-PPD均可增加p21、p27和Bax的表达，诱导PARP裂解并激活半胱天冬酶。该化合物还可降低MDM2、E2F1、Bcl2、cdk2/4/6和细胞周期蛋白D1的表达，这与细胞周期停滞于G1期及增殖减少相关。此外，25-OH-PPD对非癌细胞毒性较低，单独使用或与传统疗法联合使用时在动物中均未观察到明显的宿主毒性。
新鉴定的人参皂苷25-OH-PPD可能具有作为新型前列腺癌治疗药物的潜力。
