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${\alpha}$-Mangostin Reduced ER Stress-mediated Tumor Growth through Autophagy Activation

  • Kim, Sung-Jin (Laboratory of Immunology and Microbiology, College of Pharmacy, Kangwon National University) ;
  • Hong, Eun-Hye (Laboratory of Immunology and Microbiology, College of Pharmacy, Kangwon National University) ;
  • Lee, Bo-Ra (Laboratory of Immunology and Microbiology, College of Pharmacy, Kangwon National University) ;
  • Park, Moon-Ho (Laboratory of Immunology and Microbiology, College of Pharmacy, Kangwon National University) ;
  • Kim, Ji-Won (Laboratory of Immunology and Microbiology, College of Pharmacy, Kangwon National University) ;
  • Pyun, A-Rim (Laboratory of Immunology and Microbiology, College of Pharmacy, Kangwon National University) ;
  • Kim, Yeon-Jeong (Laboratory of Immunology and Microbiology, College of Pharmacy, Inje University) ;
  • Chang, Sun-Young (Laboratory of Immunology and Microbiology, College of Pharmacy, Ajou University) ;
  • Chin, Young-Won (Laboratory of Immunology and Microbiology, College of Pharmacy, Dongguk University) ;
  • Ko, Hyun-Jeong (Laboratory of Immunology and Microbiology, College of Pharmacy, Kangwon National University)
  • Received : 2012.10.23
  • Accepted : 2012.11.07
  • Published : 2012.12.31

Abstract

${\alpha}$-Mangostin is a xanthon derivative contained in the fruit hull of mangosteen (Garcinia mangostana L.), and the administration of ${\alpha}$-Mangostin inhibited the growth of transplanted colon cancer, Her/CT26 cells which expressed Her-2/neu as tumor antigen. Although ${\alpha}$-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 ${\alpha}$-Mangostin induced autophagy activation in mouse intestinal epithelial cells, as GFP-LC3 transgenic mice were orally administered with 20 mg/kg of ${\alpha}$-Mangostin daily for three days. However, the activation of autophagy by ${\alpha}$-Mangostin did not significantly increase OVA-specific T cell proliferation. As we assessed ER stress by using XBP-1 reporter system and phosphorylation of $eIF2{\alpha}$, thapsigargin-induced ER stress was significantly reduced by ${\alpha}$-Mangostin. However, coadministration of thapsigargin with ${\alpha}$-Mangostin completely blocked the antitumor activity of ${\alpha}$-Mangostin, suggesting ER stress with autophagy blockade accelerated tumor growth in mouse colon cancer model. Thus the antitumor activity of ${\alpha}$-Mangostin can be ascribable to the autophagy activation rather than ER stress induction.

Keywords

Acknowledgement

Supported by : Ministry for Health, Welfare and Family affairs, National Research Foundation of Korea (NRF)

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