Department of Biology, Georgia State University, Atlanta, GA-30303, USA.
Carcinogenesis. 2011 Dec;32(12):1872-80. doi: 10.1093/carcin/bgr215. Epub 2011 Sep 26.
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 ∼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.
甘薯（Ipomoea batatas）叶或绿，在非洲和亚洲广泛作为蔬菜食用，是膳食多酚如花青素和酚酸的极好来源。在这里，我们表明，与包括菠菜在内的几种商业蔬菜相比，甘薯叶提取物（SPGE）具有最高的多酚含量。富含多酚的 SPGE 在一系列前列腺癌细胞系中表现出显著的抗增殖活性，同时对正常前列腺上皮细胞没有影响。从机制上讲，SPGE 扰乱细胞周期进程，降低集落形成存活能力，调节细胞周期和凋亡调节分子，并在体外和体内诱导人前列腺癌 PC-3 细胞凋亡。SPGE 诱导的凋亡具有线粒体介导的成分，该成分可被环孢菌素 A 预处理减弱。我们还观察到凋亡调节分子的改变，如 Bcl2 失活、BAX 上调、细胞色素 c 释放和下游凋亡信号的激活。SPGE 引起 DNA 降解，如通过末端脱氧核苷酸转移酶介导的 dUTP- nick-end 标记（TUNEL）染色显示 3'-DNA 末端浓度增加。此外，凋亡诱导依赖于半胱天冬酶，如半胱天冬酶底物多聚（腺苷二磷酸核糖）聚合酶的切割所示。在裸鼠中，口服 400mg/kg SPGE 可显著抑制前列腺肿瘤异种移植物的生长和进展，通过肿瘤体积测量和非侵入性实时生物发光成像显示，抑制率约为 69%。最重要的是，SPGE 对肠道和骨髓等快速分裂的正常组织没有造成任何可检测的毒性。这是首次报道甘薯叶在前列腺癌中的体外和体内抗癌活性。
