Polyphenol-rich sweet potato greens extract inhibits proliferation and induces apoptosis in prostate cancer cells in vitro and in vivo
Polyphenol-rich sweet potato greens extract inhibits proliferation and induces apoptosis in prostate cancer cells in vitro and in vivo
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DOI：
10.1093/carcin/bgr215
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发表时间：
2011-12-01
期刊：
影响因子：
4.7
通讯作者：
Aneja, Ritu
中科院分区：
文献类型：
--
作者：
Karna, Prasanthi;Gundala, Sushma R.;Aneja, Ritu
甘薯（Ipomoea batatas）叶或绿色，在非洲和亚洲作为蔬菜广泛消费，是膳食多酚如花青素和酚酸的极好来源。在这里，我们表明，甘薯绿色提取物（SPGE）具有最大的多酚含量相比，几个商业蔬菜，包括菠菜。富含多酚的SPGE在一组前列腺癌细胞系中发挥显着的抗增殖活性，同时保留正常的前列腺上皮细胞。在机制上，SPGE干扰细胞周期进程，降低克隆存活率，调节细胞周期和凋亡调控分子，并在体外和体内诱导人前列腺癌PC-3细胞凋亡。SPGE诱导的细胞凋亡有一个细胞介导的成分，这是减弱预处理环孢素A。我们还观察到凋亡调节分子的改变，如Bcl 2的失活，BAX的上调，细胞色素c的释放和下游凋亡信号的激活。末端脱氧核苷酸转移酶介导的dUTP-nick-end labeling（TUNEL）染色显示3 '-DNA末端浓度增加，证明SPGE导致DNA降解。此外，凋亡诱导是半胱天冬酶依赖性的，如半胱天冬酶底物聚（腺苷二磷酸-核糖）聚合酶的裂解所示。如肿瘤体积测量和非侵入性实时生物发光成像所示，口服400 mg/kg SPGE显著抑制前列腺肿瘤异种移植物的生长和进展，在裸鼠中抑制率接近69%。最重要的是，SPGE不会对快速分裂的正常组织（如肠道和骨髓）造成任何可检测的毒性。这是第一份证明甘薯绿色在前列腺癌中的体外和体内抗癌活性的报告。
Sweet potato (Ipomoea batatas) leaves or greens, extensively consumed as a vegetable in Africa and Asia, are an excellent source of dietary polyphenols such as anthocyanins and phenolic acids. Here, we show that sweet potato greens extract (SPGE) has the maximum polyphenol content compared with several commercial vegetables including spinach. The polyphenol-rich SPGE exerts significant antiproliferative activity in a panel of prostate cancer cell lines while sparing normal prostate epithelial cells. Mechanistically, SPGE perturbed cell cycle progression, reduced clonogenic survival, modulated cell cycle and apoptosis regulatory molecules and induced apoptosis in human prostate cancer PC-3 cells both in vitro and in vivo. SPGE-induced apoptosis has a mitochondrially mediated component, which was attenuated by pretreatment with cyclosporin A. We also observed alterations of apoptosis regulatory molecules such as inactivation of Bcl2, upregulation of BAX, cytochrome c release and activation of downstream apoptotic signaling. SPGE caused DNA degradation as evident by terminal deoxynucleotidyl transferase-mediated dUTP-nick-end labeling (TUNEL) staining of increased concentration of 3'-DNA ends. Furthermore, apoptotic induction was caspase dependent as shown by cleavage of caspase substrate, poly (adenosine diphosphate-ribose) polymerase. Oral administration of 400 mg/kg SPGE remarkably inhibited growth and progression of prostate tumor xenografts by similar to 69% in nude mice, as shown by tumor volume measurements and non-invasive real-time bioluminescent imaging. Most importantly, SPGE did not cause any detectable toxicity to rapidly dividing normal tissues such as gut and bone marrow. This is the first report to demonstrate the in vitro and in vivo anticancer activity of sweet potato greens in prostate cancer.