天花粉蛋白通过增加颗粒酶B对肿瘤细胞的渗透来诱导抗癌作用

Yinxin Zhu, D. Ye, Jing Shen, Zhangang Xiao
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引用次数: 0

摘要

天花粉蛋白(Trichosanthin, TCS)是一种植物毒素,在临床上被用作中期堕胎药物,目前有报道称其具有抗肿瘤、抗hiv和免疫调节等其他生物和药物作用。TCS被发现能使真核细胞的核糖体失活,但这一发现足以解释其各种生物学和药物作用。我们之前的研究主要集中在探索新的TCS结合蛋白,以揭示其在哺乳动物细胞中的新机制。我们发现TCS和阳离子非依赖性甘露糖-6-磷酸受体(CI-MPR)与高尔基定位蛋白、含γ-耳蛋白和arf结合蛋白(GGA)竞争性结合,最终增加颗粒酶B的细胞通透性,促进细胞毒性T淋巴细胞介导的肿瘤细胞凋亡。
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Trichosanthin induces anti-cancer effects by increasing the penetration of Granzyme B into tumor cells
Trichosanthin (TCS), known as a plant toxin, is applied as a midterm abortifacient in clinics, and currently reported to exhibit other biological and pharmaceutical effects such as anti-tumor, anti-HIV, and Immunoregulation. TCS was found out to firmly inactivate the ribosomes of the eukaryotic cell, but this finding was far enough to explain its various biological and pharmaceutical effects. Our previous studies focused on exploring novel TCS binding proteins, as to reveal new mechanisms in mammalian cells. And we found out that TCS and cation-independent mannose-6-phosphate receptor (CI-MPR) competitively bind to Golgi-localized, γ-ear containing and Arf-binding proteins (GGA), which finally increased the cell permeability of Granzyme B and promoted the cytotoxic T lymphocyte-mediated tumor cell apoptosis.
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