title: α-Mangostin Reduced ER Stress-mediated Tumor Growth through Autophagy Activation.
abstract: α-Mangostin is a xanthon derivative contained in the fruit hull of mangosteen (Garcinia mangostana L.), and the administration of α-Mangostin inhibited the growth of transplanted colon cancer, Her/CT26 cells which expressed Her-2/neu as tumor antigen. Although α-Mangostin was reported to have inhibitory activity against sarco/endoplasmic reticulum Ca(2+) ATPase like thapsigargin, it showed different activity for autophagy regulation. In the current study, we found that α-Mangostin induced autophagy activation in mouse intestinal epithelial cells, as GFP-LC3 transgenic mice were orally administered with 20 mg/kg of α-Mangostin daily for three days. However, the activation of autophagy by α-Mangostin did not significantly increase OVA-specific T cell proliferation. As we assessed ER stress by using XBP-1 reporter system and phosphorylation of eIF2α, thapsigargin-induced ER stress was significantly reduced by α-Mangostin. However, coadministration of thapsigargin with α-Mangostin completely blocked the antitumor activity of α-Mangostin, suggesting ER stress with autophagy blockade accelerated tumor growth in mouse colon cancer model. Thus the antitumor activity of α-Mangostin can be ascribable to the autophagy activation rather than ER stress induction.
authors: Laboratory of Immunology and Microbiology, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea.
authors: Sung-Jin
authors: SJ
authors: Kim
authors: Eun-Hye
authors: EH
authors: Hong
authors: Bo-Ra
authors: BR
authors: Lee
authors: Moon-Ho
authors: MH
authors: Park
authors: Ji-Won
authors: JW
authors: Kim
authors: A-Rim
authors: AR
authors: Pyun
authors: Yeon-Jeong
authors: YJ
authors: Kim
authors: Sun-Young
authors: SY
authors: Chang
authors: Young-Won
authors: YW
authors: Chin
authors: Hyun-Jeong
authors: HJ
authors: Ko
keywords: Antitumor activity; Autophagy; Colon cancer; ER stress; Thapsigargin; α-Mangostin
references: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466-70
references: 2138778
references: Mol Cell. 2011 Jun 24;42(6):731-43
references: 21700220
references: Science. 2010 Dec 3;330(6009):1344-8
references: 21127245
references: Gastroenterology. 2011 May;140(6):1738-47
references: 21530740
references: Bioorg Med Chem. 2007 Aug 15;15(16):5620-8
references: 17553685
references: Nat Med. 2004 Jan;10(1):98-102
references: 14702639
references: J Agric Food Chem. 2011 Mar 9;59(5):2086-96
references: 21314123
references: World J Gastroenterol. 2011 Apr 28;17(16):2086-95
references: 21547127
references: Nat Rev Drug Discov. 2008 Dec;7(12):1013-30
references: 19043451
references: Mol Cell Biol. 2006 Dec;26(24):9517-32
references: 17030613
references: Phytother Res. 2010 Oct;24(10):1575-7
references: 20878711
references: Bioorg Med Chem. 2004 Nov 15;12(22):5799-806
references: 15498656
references: Mol Biol Cell. 2004 Mar;15(3):1101-11
references: 14699058
references: Jpn J Pharmacol. 1996 Aug;71(4):337-40
references: 8886932
references: Cancer Res. 2012 Jul 15;72(14):3535-45
references: 22745370
references: Trends Immunol. 2005 Oct;26(10):523-8
references: 16099218
references: Semin Immunol. 2009 Jun;21(3):156-63
references: 19237300
references: Eur J Immunol. 2012 Mar;42(3):618-28
references: 22105301
references: Genes Dev. 2009 Oct 1;23(19):2294-306
references: 19762508
references: Gastroenterology. 2010 Apr;138(4):1468-78, 1478.e1-6
references: 19914251
references: Immunity. 2010 Feb 26;32(2):227-39
references: 20171125
references: Nature. 2008 Feb 28;451(7182):1069-75
references: 18305538
references: Int J Cancer. 2008 Jun 15;122(12):2774-83
references: 18338753
references: Cell Death Differ. 2007 Feb;14(2):230-9
references: 16794605
references: Mol Cell Biol. 2006 Dec;26(24):9220-31
references: 17030611
references: J Pharmacol Sci. 2004 May;95(1):33-40
references: 15153648
references: EMBO J. 2005 Oct 5;24(19):3470-81
references: 16148948