西兰花衍生的硫代葡萄糖苷，萝卜硫素，在巴雷特腺癌中的抗癌活性：在化学预防和作为化疗辅助剂方面的潜在用途。
Anticancer activity of a broccoli derivative, sulforaphane, in barrett adenocarcinoma: potential use in chemoprevention and as adjuvant in chemotherapy.
机构信息
Departments of Surgery/Obstetrics and Gynecology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
出版信息
Transl Oncol. 2010 Dec 1;3(6):389-99. doi: 10.1593/tlo.10235.
INTRODUCTION
The incidence of Barrett esophageal adenocarcinoma (BEAC) has been increasing at an alarming rate in western countries. In this study, we have evaluated the therapeutic potential of sulforaphane (SFN), an antioxidant derived from broccoli, in BEAC.
METHODS
BEAC cells were treated with SFN, alone or in combination with chemotherapeutic, paclitaxel, or telomerase-inhibiting agents (MST-312, GRN163L), and live cell number determined at various time points. The effect on drug resistance/chemosensitivity was evaluated by rhodamine efflux assay. Apoptosis was detected by annexin V labeling and Western blot analysis of poly(ADP-ribose) polymerase cleavage. Effects on genes implicated in cell cycle and apoptosis were determined by Western blot analyses. To evaluate the efficacy in vivo, BEAC cells were injected subcutaneously in severe combined immunodeficient mice, and after the appearance of palpable tumors, mice were treated with SFN.
RESULTS
SFN induced both time- and dose-dependent decline in cell survival, cell cycle arrest, and apoptosis. The treatment with SFN also suppressed the expression of multidrug resistance protein, reduced drug efflux, and increased anticancer activity of other antiproliferative agents including paclitaxel. A significant reduction in tumor volume was also observed by SFN in a subcutaneous tumor model of BEAC. Anticancer activity could be attributed to the induction of caspase 8 and p21 and down-regulation of hsp90, a molecular chaperon required for activity of several proliferation-associated proteins.
CONCLUSIONS
These data indicate that a natural product with antioxidant properties from broccoli has great potential to be used in chemoprevention and treatment of BEAC.
简介
在西方国家，巴雷特食管腺癌（BEAC）的发病率呈惊人的速度增长。在这项研究中，我们评估了来自西兰花的抗氧化剂——萝卜硫素（SFN）在 BEAC 中的治疗潜力。
方法
BEAC 细胞用 SFN 单独或与化疗药物紫杉醇或端粒酶抑制剂（MST-312、GRN163L）联合处理，并在不同时间点测定活细胞数。通过罗丹明外排测定评估对耐药性/化疗敏感性的影响。通过 Annexin V 标记和聚（ADP-核糖）聚合酶切割的 Western blot 分析检测细胞凋亡。通过 Western blot 分析确定与细胞周期和细胞凋亡相关的基因的影响。为了评估体内疗效，将 BEAC 细胞皮下注射入严重联合免疫缺陷小鼠中，在可触及肿瘤出现后，用 SFN 治疗小鼠。
结果
SFN 诱导时间和剂量依赖性的细胞存活、细胞周期停滞和细胞凋亡。SFN 的治疗还抑制了多药耐药蛋白的表达，减少了药物外排，并增加了包括紫杉醇在内的其他抗增殖药物的抗癌活性。SFN 还在 BEAC 的皮下肿瘤模型中显著减少了肿瘤体积。抗癌活性可归因于 caspase 8 和 p21 的诱导以及分子伴侣 hsp90 的下调，hsp90 是几种与增殖相关蛋白活性所必需的。
结论
这些数据表明，来自西兰花的具有抗氧化特性的天然产物具有很大的潜力，可用于 BEAC 的化学预防和治疗。
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