Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America ; University of Illinois Cancer Center, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
PLoS One. 2013 Dec 18;8(12):e81572. doi: 10.1371/journal.pone.0081572. eCollection 2013.
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.
癌细胞的增殖增加直接依赖于内质网（ER）机制的活性增加，内质网负责蛋白质折叠、组装和运输。事实上，内质网的波动如此关键，以至于可能导致细胞凋亡。这个经过精心调节的细胞器代表了癌细胞的独特靶点，同时对健康细胞没有影响。在这项研究中，标准化的山竹果提取物（MFE）被评估用于调节前列腺癌中的内质网应激蛋白。用 MFE 处理从两名接受根治性前列腺切除术的患者中获得的两种人前列腺癌细胞系 22Rv1 和 LNCaP 以及前列腺上皮细胞（PrEC）。流式细胞术、MTT、BrdU 和 Western blot 用于评估细胞凋亡、活力、增殖和内质网应激。接下来，我们评估了 MFE 在裸鼠中的微粒体稳定性和抗癌活性。MFE 诱导前列腺癌细胞凋亡，降低活力和增殖。MFE 增加了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中的内质网应激，同时对 PrEC 没有影响。MFE 在异种移植肿瘤模型中抑制肿瘤生长，没有明显的毒性。山竹果提取物选择性地促进癌细胞中的内质网应激，同时对非肿瘤性前列腺上皮细胞没有影响。此外，在体内环境中，山竹果提取物显著减少了异种移植肿瘤的形成。
