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KMID : 0923620120120060253
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Immune Network
2012 Volume.12 No. 6 p.253 ~ p.260
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α-Mangostin Reduced ER Stress-mediated Tumor Growth through Autophagy Activation
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Kim Sung-Jin
Hong Eun-Hye
Lee Bo-Ra
Park Moon-Ho
Kim Ji-Won
Pyun A-Rim
Kim Yeon-Jeong
Chang Sun-Young
Chin Young-Won
Ko Hyun-Jeong
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Abstract
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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 ?-Mangostin was reported to have inhibitory activity against sarco/endoplasmic reticulum Ca2+ 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 ?-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 ?-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.
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KEYWORD
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Autophagy, α-Mangostin, Thapsigargin, ER stress, Antitumor activity, Colon cancer
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