title: Inhibition of CHOP accentuates the apoptotic effect of α-mangostin from the mangosteen fruit (Garcinia mangostana) in 22Rv1 prostate cancer cells.
abstract: The mangosteen (Garcinia mangostana) fruit has been a popular food in Southeast Asia for centuries and is increasing in popularity in Western countries. We identified α-Mangostin as a primary phytochemical modulating ER stress proteins in prostate cancer cells and propose that α-Mangostin is responsible for exerting a biological effect in prostate cancer cells. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two patients undergoing radical prostatectomy were treated with α-Mangostin and evaluated by RT-PCR, Western blot, fluorescent microscopy and siRNA transfection to evaluate ER stress. Next, we evaluated α-Mangostin for microsomal stability, pharmacokinetic parameters, and anti-cancer activity in nude mice. α-Mangostin significantly upregulated ER stress markers in prostate cancer cells. Interestingly, α-Mangostin did not promote ER stress in prostate epithelial cells (PrECs) from prostate cancer patients. CHOP knockdown enhanced α-Mangostin-induced apoptosis in prostate cancer cells. α-Mangostin significantly suppressed tumor growth in a xenograft tumor model without obvious toxicity. Our study suggests that α-Mangostin is not the only active constituent from the mangosteen fruit requiring further work to understand the complex chemical composition of the mangosteen.
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Department of Pharmacy Practice, United States.
authors.forename: Gongbo
authors.initials: G
authors.lastname: Li
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Department of Pharmacy Practice, United States.
authors.forename: Sakina M
authors.initials: SM
authors.lastname: Petiwala
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Department of Pathology, United States; University of Illinois Cancer Center, United States.
authors.forename: Larisa
authors.initials: L
authors.lastname: Nonn
authors.affiliation: University of Illinois at Chicago, College of Pharmacy, Department of Pharmacy Practice, United States; University of Illinois Cancer Center, United States. Electronic address: jjjohn@uic.edu.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D004355:Drug Stability; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005638:Fruit / Q000737:chemistry; D029762:Garcinia mangostana / Q000737:chemistry; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008862:Microsomes, Liver / Q000378:metabolism; D008517:Phytotherapy; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051742:Transcription Factor CHOP / Q000037:antagonists & inhibitors* / Q000235:genetics; D044004:Xanthones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497249:DDIT3 protein, human; D044004:Xanthones; D051742:Transcription Factor CHOP; C021053:mangostin
keywords: CHOP; ER stress; Mangosteen; Mangostin; Prostate cancer; Xanthone