title: Selective modulation of endoplasmic reticulum stress markers in prostate cancer cells by a standardized mangosteen fruit extract.
abstract: 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.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Gongbo
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Sakina M
authors.initials: SM
authors.lastname: Petiwala
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Dana R
authors.initials: DR
authors.lastname: Pierce
authors.affiliation: 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.
authors.forename: Larisa
authors.initials: L
authors.lastname: Nonn
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, 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.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005638:Fruit / Q000737:chemistry*; D029762:Garcinia mangostana / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D010936:Plant Extracts