Journal of Cellular & Molecular Medicine, 2012, 16(11):2631-6.

Anticancer activities of genistein-topotecan combination in prostate cancer cells

Vanessa Hörmann, James Kumi-Diaka, Marcia Durity, et al

Department of Biological Sciences, Florida Atlantic University, Davie, FL, USA; et al

Prostate cancer is one of the leading causes of death in men aged 40 to 55. Genistein isoflavone (4', 5', 7-trihydroxyisoflavone) is a dietary phytochemical with demonstrated anti-tumour activities in a variety of cancers. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy drug, primarily used for secondary treatment of ovarian, cervical and small cell lung cancers. This study was to demonstrate the potential anticancer efficacy of genistein-topotecan combination in LNCaP prostate cancer cells and the mechanism of the combination treatment. The LNCaP cells were grown in complete RPMI medium, and cultured at 37°C, 5% CO(2) for 24-48 hrs to achieve 70-90% confluency. The cells were treated with varying concentrations of genistein, topotecan and genistein-topotecan combination and incubated for 24 hrs. The treated cells were assayed for (i) post-treatment sensitivity using MTT assay and DNA fragmentation, (ii) treatment-induced apoptosis using caspase-3 and -9 binding assays and (iii) treatment-induced ROS generation levels. The overall data indicated that (i) both genistein and topotecan induce cellular death in LNCaP cells, (ii) genistein-topotecan combination was significantly more efficacious in reducing LNCaP cell viability compared with either genistein or topotecan alone, (iii) in all cases, cell death was primarily through apoptosis, via the activation of caspase-3 and -9, which are involved in the intrinsic pathway, (iv) ROS generation levels increased significantly with the genistein-topotecan combination treatment. Treatments involving genistein-topotecan combination may prove to be an attractive alternative phytotherapy or adjuvant therapy for prostate cancer.

英国《细胞与分子医学杂志》，2012年11月

金雀异黄素-拓扑替康组合在前列腺癌细胞中的抗肿瘤活性

凡妮莎 霍曼，詹姆斯 久美 迪亚卡，玛西娅 杜瑞缇，等

美国佛罗里达大西洋大学生物科学学院等

前列腺癌是年龄在 40 到 55 岁男性死亡的原因之一。金雀异黄素异黄酮 （4'，5'，7-三羟基异黄酮） 是一种饮食植物化学成分，对多种癌症表现出抗肿瘤活性。盐酸拓扑替康 （盐酸拓扑替康） 是美国 FDA 批准的化疗药物，主要用于卵巢癌、 宫颈癌和小细胞肺癌的辅助治疗。本研究旨在证明金雀异黄素-拓扑替康联合治疗对LNCaP 前列腺癌细胞的潜在抗癌作用和治疗机理。LNCaP 细胞在完整的 RPMI 介质中生长，在 37 ° C，5 % CO（2) 的条件下培养 24-48 小时达到 70-90%的饱和。用不同浓度的金雀异黄素、 拓扑替康、 金雀异黄素-拓扑替康组合物处理并孵化细胞24 小时。（i）采用 MTT 法和 DNA 碎片检测治疗后的灵敏度，（ii）使用半胱氨酸蛋白酶-3 和-9 检测治疗诱导的细胞凋亡以及 （iii） 治疗诱导的活性氧生成水平测定处理后的细胞。整体的数据表明，（i） 金雀异黄素和拓扑替康都可以诱导LNCaP 细胞死亡，（ii） 金雀异黄素-拓扑替康组合与单独的金雀异黄素或拓扑替康相比能够明显更有效地减少 LNCaP 细胞的生存能力，（iii） 在所有情况下，细胞死亡主要是通过细胞凋亡，通过半胱氨酸蛋白酶-3 和-9的活性等固定的通路 ，（iv) 由于金雀异黄素-拓扑替康的联合治疗 ROS 生成水平明显增加。含有金雀异黄素-拓扑替康组合的治疗方法被证明可能是一种有吸引力的治疗前列腺癌的替代植物疗法或辅助疗法。