Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract.
Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract.
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DOI：
10.1371/journal.pone.0081572
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Johnson JJ
中科院分区：
文献类型：
--
作者：
Li G;Petiwala SM;Pierce DR;Nonn L;Johnson JJ
癌细胞增殖的增加直接依赖于负责蛋白质折叠、组装和运输的内质网(ER)机制的活性增加。事实上，它是如此关键，内质网的扰动可能会导致细胞凋亡。这种精心调控的细胞器代表了癌细胞的独特靶点，同时又保留了健康细胞。在这项研究中，一种标准化的山竹果提取物(MFE)被用来调节前列腺癌中的ER应激蛋白。用MFE处理两株人前列腺癌细胞系22Rv1和LNCaP，以及两例前列腺癌根治术患者的前列腺癌上皮细胞(PrECs)。采用流式细胞仪、四甲基偶氮唑蓝、BrdU和Western印迹等方法检测细胞的凋亡率、存活率、增殖率和内质网应激。接下来，我们评估了MFE在裸鼠体内的微粒体稳定性和抗癌活性。MFE诱导前列腺癌细胞凋亡，细胞存活率和增殖率下降。MFE可增加内质网应激蛋白的表达。有趣的是，MFE选择性地促进前列腺癌细胞的内质网应激，而不影响前内皮细胞。在无明显毒性的异种移植瘤模型中，MFE可抑制肿瘤生长。山竹果提取物选择性地促进癌细胞的内质网应激，而不影响非致癌的前列腺上皮细胞。此外，在体内实验中，山竹果提取物显著减少了异种移植瘤的形成。
The increased proliferation of cancer cells is directly dependent on the increased activity of the endoplasmic reticulum (ER) machinery which is responsible for protein folding, assembly, and transport. In fact, it is so critical that perturbations in the endoplasmic reticulum can lead to apoptosis. This carefully regulated organelle represents a unique target of cancer cells while sparing healthy cells. In this study, a standardized mangosteen fruit extract (MFE) was evaluated for modulating ER stress proteins in prostate cancer. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells (PrECs) procured from two patients undergoing radical prostatectomy were treated with MFE. Flow cytometry, MTT, BrdU and Western blot were used to evaluate cell apoptosis, viability, proliferation and ER stress. Next, we evaluated MFE for microsomal stability and anti-cancer activity in nude mice. MFE induced apoptosis, decreased viability and proliferation in prostate cancer cells. MFE increased the expression of ER stress proteins. Interestingly, MFE selectively promotes ER stress in prostate cancer cells while sparing PrECs. MFE suppressed tumor growth in a xenograft tumor model without obvious toxicity. Mangosteen fruit extract selectively promotes endoplasmic reticulum stress in cancer cells while sparing non-tumorigenic prostate epithelial cells. Furthermore, in an in vivo setting mangosteen fruit extract significantly reduces xenograft tumor formation.
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影响因子：
7.8
作者：
Hitomi, Junichi;Katayama, Taiichi;Eguchi, Yutaka;Kudo, Takashi;Taniguchi, Manabu;Koyama, Yoshihisa;Manabe, Takayuki;Yamagishi, Satoru;Bando, Yoshio;Imaizumi, Kazunori;Tsujimoto, Yoshihide;Tohyama, Masaya
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DOI：
10.1083/jcb.201110131
发表时间：
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期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
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DOI：
10.1007/978-1-60761-756-3_1
发表时间：
2010-01-01
期刊：
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影响因子：
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作者：
Gregersen, Niels;Bross, Peter
通讯作者：
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影响因子：
2.6
作者：
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