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Superoxide anion and proteasomal dysfunction contribute to curcumin-induced paraptosis of malignant breast cancer cells

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Author(s)
Mi Jin YoonEun Hee KimJun Hee LimTaeg Kyu KwonKyeong Sook Choi
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Free Radical Biology and Medicine
Issued Date
2010
Volume
48
Issue
5
Abstract
Curcumin is considered a pharmacologically safe agent that may be useful in cancer chemoprevention and
therapy. Here, we show for the first time that curcumin effectively induces paraptosis in malignant breast
cancer cell lines, including MDA-MB-435S, MDA-MB-231, and Hs578T cells, by promoting vacuolation that
results from swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). Inhibition of
protein synthesis by cycloheximide blocked curcumin-induced vacuolation and subsequent cell death,
indicating that protein synthesis is required for this process. The levels of AIP-1/Alix protein, a known
inhibitor protein of paraptosis, were progressively downregulated in curcumin-treated malignant breast
cancer cells, and AIP-1/Alix overexpression attenuated curcumin-induced death in these cells. ERK2 and JNK
activation were positively associated with curcumin-induced cell death. Mitochondrial superoxide was
shown to act as a critical early signal in curcumin-induced paraptosis, whereas proteasomal dysfunction was
mainly responsible for the paraptotic changes associated with ER dilation. Notably, curcumin-induced
paraptotic events were not observed in normal breast cells, including mammary epithelial cells and MCF-10A
cells. Taken together, our findings on curcumin-induced paraptosis may provide novel insights into the
mechanisms underlying the selective anti-cancer effects of curcumin against malignant cancer cells.
Crown Copyright © 2009 Published by Elsevier Inc. All rights reserved
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Mi Jin Yoon et al. (2010). Superoxide anion and proteasomal dysfunction contribute to curcumin-induced
paraptosis of malignant breast cancer cells. Free Radical Biology and Medicine, 48(5), 713–726. doi: 10.1016/j.freeradbiomed.2009.12.016
Type
Article
ISSN
0891-5849
Source
http://lps3.linkinghub.elsevier.com.proxy.dsmc.or.kr/retrieve/pii/S0891-5849(09)00787-4
DOI
10.1016/j.freeradbiomed.2009.12.016
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35755
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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