Lu Xiaohua, Guo Junqiao, Hsieh Tze-Chen, Wu Joseph M
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Anticancer Res. 2003 May-Jun;23(3B):2489-98.
Use of dietary supplements and botanical products is widely accepted by patients diagnosed with prostate cancer (CaP) as a primary or complementary form of treatment for their medical conditions in the U.S. Yet, the majority of these products have not been rigorously studied with regard to scientific mechanism(s). Because many of the available products are mixtures of multiple extracts derived from plants, some of which are not necessarily native to the U.S., we consider mechanistic studies under defined laboratory conditions to be valuable and essential, not only from the standpoint of standardization and possible contamination with the products, but also in providing insights and scientific evidence for the clinical efficacy some of these products purportedly demonstrate. In previous studies from this laboratory, Equiguard, a composite supplement consisting of standardized extracts from nine Chinese herbs, which was originally formulated to correct physiological decline in kidney functions associated with age, was fortuitously found to display anti-CaP properties. Using a panel of CaP cells, we showed that ethanol extracts of Equiguard significantly inhibited cancer cell growth, induced apoptosis, lowered expression of the androgen receptor (AR), decreased intracellular and secreted prostate-specific antigen (PSA) levels and completely abolished the colony forming activities of CaP cells. Since responsiveness to Equiguard was observed in cells mimicking the androgen-dependent (AD) and androgen-independent (AI) states of CaP, our results raise the interesting possibility that this herbal supplement may potentially prevent, delay or circumvent the onset of AI, and thereby induce chronic instead of terminal CaP. Since androgen ablation therapy (chemical or surgical castration) is the mainstay for localized CaP, we questioned whether Equiguard might still exert the aforementioned activities in experimental settings modeled after androgen ablation. Accordingly, we studied the effects of Equiguard in LNCaP cells, cultured in androgen-proficient (FBS) or -deficient (CS-FBS) media that simulate the hormonal status pre- and post-castration in vivo. Extracts of Equiguard were effective in reducing colony formation, proliferation and PCNA expression of cells cultured in CS-FBS. Moreover, within a concentration range of Equiguard, the prostate-specific genes, PSA and AR, were affected to a similar extent in cells cultured either in FBS or CS-FBS, and were correlated with increased phosphorylation at serine-15 of the tumor suppressor gene p53. These results are consistent with the interpretation that the anti-proliferative and gene modulatory properties of Equiguard are largely independent of the status of androgens in the culture media.
在美国，膳食补充剂和植物产品作为原发性或补充性治疗方式被前列腺癌（CaP）患者广泛接受。然而，这些产品中的大多数尚未针对其科学机制进行严格研究。由于许多现有产品是多种植物提取物的混合物，其中一些并非原产于美国，我们认为在明确的实验室条件下进行机制研究不仅从产品标准化和可能的污染角度来看是有价值且必不可少的，而且还能为这些产品据称所展示的临床疗效提供见解和科学证据。在本实验室之前的研究中，Equiguard是一种由九种中药标准化提取物组成的复合补充剂，最初旨在纠正与年龄相关的肾功能生理衰退，偶然发现它具有抗CaP特性。我们使用一组CaP细胞表明，Equiguard的乙醇提取物显著抑制癌细胞生长、诱导凋亡、降低雄激素受体（AR）的表达、降低细胞内和分泌的前列腺特异性抗原（PSA）水平，并完全消除CaP细胞的集落形成活性。由于在模拟CaP雄激素依赖（AD）和雄激素非依赖（AI）状态的细胞中观察到了对Equiguard的反应，我们的结果提出了一个有趣的可能性，即这种草药补充剂可能潜在地预防、延迟或规避AI的发生，从而诱导慢性而非晚期CaP。由于雄激素剥夺疗法（化学或手术去势）是局限性CaP的主要治疗方法，我们质疑Equiguard在模拟雄激素剥夺的实验环境中是否仍能发挥上述作用。因此，我们研究了Equiguard在LNCaP细胞中的作用，这些细胞在富含雄激素（FBS）或缺乏雄激素（CS - FBS）的培养基中培养，分别模拟体内去势前后的激素状态。Equiguard提取物能有效减少在CS - FBS中培养的细胞的集落形成、增殖和PCNA表达。此外，在Equiguard的浓度范围内，前列腺特异性基因PSA和AR在FBS或CS - FBS中培养的细胞中受到的影响程度相似，并且与肿瘤抑制基因p53丝氨酸 - 15位点磷酸化增加相关。这些结果与以下解释一致，即Equiguard的抗增殖和基因调节特性在很大程度上与培养基中的雄激素状态无关。
