title: α-Mangostin inhibits hypoxia-driven ROS-induced PSC activation and pancreatic cancer cell invasion.
abstract: Recent advances indicating a key role of microenvironment for tumor progression, we investigated the role of PSCs and hypoxia in pancreatic cancer aggressiveness, and examined the potential protective effect of α-mangostin on hypoxia-driven pancreatic cancer progression. Our data indicate that hypoxic PSCs exploit their oxidative stress due to hypoxia to secrete soluble factors favouring pancreatic cancer invasion. α-Mangostin suppresses hypoxia-induced PSC activation and pancreatic cancer cell invasion through the inhibition of HIF-1α stabilization and GLI1 expression. Increased generation of hypoxic ROS is responsible for HIF-1α stabilization and GLI1 upregulation. Therefore, α-mangostin may be beneficial in preventing hypoxia-induced pancreatic cancer progression.
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Jianjun
authors: J
authors: Lei
authors: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Xiongwei
authors: X
authors: Huo
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Wanxing
authors: W
authors: Duan
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Qinhong
authors: Q
authors: Xu
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Rong
authors: R
authors: Li
authors: Department of Oncology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Jiguang
authors: J
authors: Ma
authors: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Xuqi
authors: X
authors: Li
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Liang
authors: L
authors: Han
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China.
authors: Wei
authors: W
authors: Li
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China. Electronic address: sunhaoxjyf@126.com.
authors: Hao
authors: H
authors: Sun
authors: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, USA.
authors: Erxi
authors: E
authors: Wu
authors: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China. Electronic address: qyma56@mail.xjtu.edu.cn.
authors: Qingyong
authors: Q
authors: Ma
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000166:cytology* / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D044004:Xanthones; D000071676:Zinc Finger Protein GLI1; C021053:mangostin
keywords: Hypoxia; PSC; Pancreatic cancer; ROS; α-Mangostin