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首页> 外文期刊>Journal of Agricultural and Food Chemistry >The Tomato Glycoalkaloid alpha-Tomatine Induces Caspase-Independent Cell Death in Mouse Colon Cancer CT-26 Cells and Transplanted Tumors in Mice
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The Tomato Glycoalkaloid alpha-Tomatine Induces Caspase-Independent Cell Death in Mouse Colon Cancer CT-26 Cells and Transplanted Tumors in Mice

机译：番茄糖生物碱α-番茄碱在小鼠结肠癌CT-26细胞和小鼠移植肿瘤中诱导胱天蛋白酶非依赖性细胞死亡。

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Tomatoes (Solanum lycopersicum) produce the bioactive glycoalkaloid alpha-tomatine. This study determined the effect of commercial alpha-tomatine on CT-26 colon cancer cells in vitro and in vivo in an intracutaneously transplanted mouse tumor. Cytotoxicity experiments showed that alpha-tomatine induces about 50% lysis of the colon cancer cells at 3.5 mu M after 24 h of treatment. Large proportions of cells were found to be in the annexin V (+)/propidium iodide (+) phase of cell death, implying late phase apoptoticecrotic status. However, alpha-tomatine induced cell death in CT-26 cancer cells through caspase-independent signaling pathways. This conclusion was supported by Western blot analysis showing a localization of apoptosis-inducing mitochondrial protein (AIF) to the nucleus and down-regulation of survivin (an inhibitor of apoptosis) expression as well as failure to detect the active form of caspase-3, -8, and -9 produced by proteolytic cleavage in CT-26 cancer cells. Intraperitoneally administered alpha-tomatine (5 mg/kg body weight) also markedly inhibited growth of the tumor using CT-26 cancer cells without causing body and organ weight changes. The reduced tumor growth in the mice by 38% after 2 weeks was the result of increased caspase-independent apoptosis associated with increased nuclear translocation of AIF and decreased survivin expression in tumor tissues. alpha-Tomatine in pure form and in tomatine-rich green tomatoes might prevent colon cancer.
机译：番茄（茄属植物）产生生物活性的糖生物碱α-番茄碱。这项研究确定了在皮肤内移植的小鼠肿瘤中，体外和体内市售α-番茄碱对CT-26结肠癌细胞的影响。细胞毒性实验显示，治疗24小时后，α-番茄碱在3.5μM的浓度下可诱导约50％的结肠癌细胞裂解。发现大部分细胞处于细胞死亡的膜联蛋白V（+）/碘化丙啶（+）阶段，这意味着晚期细胞凋亡/坏死状态。但是，α-番茄碱通过不依赖caspase的信号传导途径诱导CT-26癌细胞的细胞死亡。 Western印迹分析支持这一结论，表明凋亡诱导线粒体蛋白（AIF）定位于细胞核并下调了survivin（凋亡抑制剂）的表达，并且未能检测到caspase-3的活性形式，蛋白水解切割在CT-26癌细胞中产生的-8和-9。腹膜内给予的α-番茄碱（5 mg / kg体重）也明显抑制了使用CT-26癌细胞的肿瘤生长，而不会引起体重和器官重量的变化。 2周后小鼠体内肿瘤生长减少了38％，这是与caspase无关的凋亡增加的结果，该凋亡与AIF核转运增加和肿瘤组织中survivin表达降低有关。纯净形式和富含番茄素的绿色番茄中的α-托马汀可以预防结肠癌。

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