Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract

• Published in: PloS one 2013-12, Vol.8 (12), p.e81572-e81572
• Main Authors: Li, Gongbo, Petiwala, Sakina M, Pierce, Dana R, Nonn, Larisa, Johnson, Jeremy J
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Anticancer properties; Apoptosis; Biocompatibility; Blotting, Western; Cancer; Cancer cells; Cancer surgery; Cell culture; Cell cycle; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Cytometry; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Enzyme-Linked Immunosorbent Assay; Epithelial cells; Flow Cytometry; Fruit - chemistry; Fruits; Garcinia mangostana; Garcinia mangostana - chemistry; Heat shock proteins; Homeostasis; Humans; Leukemia; Machinery; Machinery and equipment; Male; Mice; Pharmacy; Plant Extracts - chemistry; Plant Extracts - pharmacology; Prostate cancer; Prostatectomy; Prostatic Neoplasms - metabolism; Protein folding; Protein synthesis; Protein transport; Proteins; Signal transduction; Stability analysis; Stress; Stress proteins; Toxicity; Tumor cell lines; Viability; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081572

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.