title: α-Mangostin suppresses the viability and epithelial-mesenchymal transition of pancreatic cancer cells by downregulating the PI3K/Akt pathway.
abstract: α -Mangostin, a natural product isolated from the pericarp of the mangosteen fruit, has been shown to inhibit the growth of tumor cells in various types of cancers. However, the underlying molecular mechanisms are largely unclear. Here, we report that α -mangostin suppressed the viability and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells through inhibition of the PI3K/Akt pathway. Treatment of pancreatic cancer BxPc-3 and Panc-1 cells with α -mangostin resulted in loss of cell viability, accompanied by enhanced cell apoptosis, cell cycle arrest at G1 phase, and decrease of cyclin-D1. Moreover, Transwell and Matrigel invasion assays showed that α -mangostin significantly reduced the migration and invasion of pancreatic cancer cells. Consistent with these results, α -mangostin decreased the expression of MMP-2, MMP-9, N-cadherin, and vimentin and increased the expression of E-cadherin. Furthermore, we found that α -mangostin suppressed the activity of the PI3K/Akt pathway in pancreatic cancer cells as demonstrated by the reduction of the Akt phosphorylation by α -mangostin. Finally, α -mangostin significantly inhibited the growth of BxPc-3 tumor mouse xenografts. Our results suggest that α -mangostin may be potentially used as a novel adjuvant therapy or complementary alternative medicine for the management of pancreatic cancers.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Oncology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Jiguang
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Wanxing
authors.identifier: 0000-0002-2851-2513
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Ang
authors.identifier: 0000-0002-3587-4432
authors.initials: A
authors.lastname: Hu
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA.
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Xuqi
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D044004:Xanthones; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C021053:mangostin