title: α-Mangostin: a dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model.
abstract: OBJECTIVE
  Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of α-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC.
  
  
  RESULTS
  The chemotherapeutic effect of α-mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and ASPC1). α-Mangostin resulted in a significant inhibition of PC cells viability without having any effects on normal human pancreatic duct epithelial cells. α-Mangostin showed a dose-dependent increase of apoptosis in PC cells. Also, α-mangostin inhibited the expression levels of pNF-κB/p65Ser552, pStat3Ser727, and pStat3Tyr705. α-Mangostin inhibited DNA binding activity of nuclear factor kappa B (NF-κB) and signal transducer and activator 3 (Stat3). α-Mangostin inhibited the expression levels of matrix metallopeptidase 9 (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p. administration of α-mangostin (6 mg/kg body weight, 5 days a week) resulted in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No sign of toxicity was observed in any of the mice administered with α-mangostin. α-Mangostin treatment inhibited the biomarkers of cell proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the xenograft tumor tissues.
  
  
  METHODS
  We present, for the first time, that dietary antioxidant α-mangostin inhibits the growth of PC cells in vitro and in vivo.
  
  
  CONCLUSIONS
  These results suggest the potential therapeutic efficacy of α-mangostin against human PC.
authors.affiliation: 1 Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin , Madison, Wisconsin.
authors.forename: Bilal Bin
authors.initials: BB
authors.lastname: Hafeez
authors.forename: Ala
authors.initials: A
authors.lastname: Mustafa
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Fischer
authors.forename: Ashok
authors.initials: A
authors.lastname: Singh
authors.forename: Weixiong
authors.initials: W
authors.lastname: Zhong
authors.forename: Mohammed Ozair
authors.initials: MO
authors.lastname: Shekhani
authors.forename: Louise
authors.initials: L
authors.lastname: Meske
authors.forename: Thomas
authors.initials: T
authors.lastname: Havighurst
authors.forename: KyungMann
authors.initials: K
authors.lastname: Kim
authors.forename: Ajit Kumar
authors.initials: AK
authors.lastname: Verma
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D029762:Garcinia mangostana / Q000737:chemistry*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D044004:Xanthones; C021053:mangostin