beta-carboline alkaloid-enriched extract from the amazonian rain forest tree pao pereira suppresses prostate cancer cells.

Debra L Bemis, Jillian L Capodice, Manisha Desai, Aaron E Katz, Ralph Buttyan
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Abstract

Bark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched in alpha-carboline alkaloids have significant anticancer activities in certain preclinical models. Because of the predominance of prostate cancer as a cause of cancer-related morbidity and mortality for men of Western countries, we preclinically tested the in vitro and in vivo effects of a pao pereira extract against a prototypical human prostate cancer cell line, LNCaP. When added to cultured LNCaP cells, pao pereira extract significantly suppressed cell growth in a dose-dependent fashion and induced apoptosis. Immunodeficient mice heterotopically xenografted with LNCaP cells were gavaged daily with pao pereira extract or vehicle control over 6 weeks. Tumor growth was suppressed by up to 80% in some groups compared with tumors in vehicle-treated mice. However, we observed a striking U-shaped dose-response curve in which the highest dose tested (50 mg/kg/d) was much less effective in inducing tumor cell apoptosis and in reducing tumor cell proliferation and xenograft growth compared with lower doses (10 or 20 mg/kg/d). Although this study supports the idea that a pao pereira bark extract has activity against human prostate cancer, our in vivo results suggest that its potential effectiveness in prostate cancer treatment may be limited to a narrow dose range.

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从亚马逊雨林树木中提取的富含-碳碱生物碱的提取物抑制前列腺癌细胞。
亚马逊热带雨林树Geissospermum vellosii (pao pereira)的树皮提取物富含α -碳碱生物碱,在某些临床前模型中具有显著的抗癌活性。由于前列腺癌是西方国家男性癌症相关发病率和死亡率的主要原因,我们在体外和体内测试了一种pao pereira提取物对一种典型的人类前列腺癌细胞系LNCaP的作用。当添加到培养的LNCaP细胞时,pao pereira提取物以剂量依赖的方式显著抑制细胞生长并诱导细胞凋亡。异种移植LNCaP细胞的免疫缺陷小鼠每天灌胃pao pereira提取物或对照,持续6周。与药物处理小鼠的肿瘤相比,某些组的肿瘤生长被抑制高达80%。然而,我们观察到一个惊人的u型剂量-反应曲线,其中最高剂量(50 mg/kg/d)在诱导肿瘤细胞凋亡和减少肿瘤细胞增殖和异种移植物生长方面的效果远不如低剂量(10或20 mg/kg/d)。虽然本研究支持了槟榔提取物对人类前列腺癌具有活性的观点,但我们的体内实验结果表明,其治疗前列腺癌的潜在效果可能仅限于一个狭窄的剂量范围。
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