Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model.
Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model.
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DOI：
10.1158/1940-6207.capr-11-0376
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Ray RB
中科院分区：
文献类型：
--
作者：
Ru P;Steele R;Nerurkar PV;Phillips N;Ray RB
前列腺癌仍然是美国男性癌症死亡的第二大原因。早期诊断可提高患者的生存率。然而，晚期疾病的治疗仅限于激素消融技术和姑息治疗。因此，需要新的治疗和预防方法来抑制疾病进展为激素难治性状态。控制前列腺癌的方法之一是通过饮食预防，其抑制一种或多种肿瘤事件并降低癌症风险。几个世纪以来，阿育吠陀一直推荐使用苦瓜（Momorea charantia）作为预防和治疗人类健康相关问题的功能性食品。在这项研究中，我们最初使用人前列腺癌细胞，PC 3和LNCaP，作为体外模型，以评估苦瓜提取物（BME）作为抗癌剂的疗效。我们观察到BME处理的前列腺癌细胞在细胞周期的S期积累，并调节cyclin D1，cyclin E和p21的表达。用BME处理前列腺癌细胞增强Bax表达，并诱导聚（ADP-核糖）聚合酶裂解。口服灌胃BME，作为一种饮食化合物，延缓了TRAMP（小鼠前列腺转基因腺癌）小鼠（31%）向高级别前列腺上皮内瘤（PIN）的进展。BME喂养小鼠的前列腺组织显示PCNA表达减少约51%。总之，我们的研究结果首次表明，口服BME通过干扰细胞周期进展和增殖抑制TRAMP小鼠中的前列腺癌进展。
Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation.