Costunolide Induces Apoptosis in Human Endometriotic Cells through Inhibition of the Prosurvival Akt and Nuclear Factor Kappa B Signaling Pathway
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概要
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Endometriosis, a disease affecting 5—15% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue. Costunolide, a sesquiterpene lactone, has anti-proliferative and pro-apoptotic activities that may be efficacious in therapy for endometriosis. In the present study, we investigated the effect of costunolide on the cell growth and apoptosis of endometriotic cells. We found that costunolide significantly inhibited the cell viability of 11Z and 12Z human endometriotic epithelial cells. Interestingly, endometriotic cells were more sensitive to costunolide treatment than immortalized endometrial cells (HES). Costunolide induced apoptosis of 11Z cells in a time-dependent manner as shown by accumulation of sub-G1 population. In addition, treatment with costunolide induced the activation of caspase-3, -8, and -9 in a dose- and time-dependent manner. Pretreatment with the broad caspase inhibitor z-VAD-fmk significantly reversed the costunolide-induced inhibition of cell viability in 11Z cells. We further demonstrated that costunolide inhibited the activation of Akt and nuclear factor kappa B (NFκB) and the expression of anti-apoptotic factors B-cell lymphoma-extra lage (Bcl-xL) and X-linked inhibitor of apoptosis protein (XIAP) in 11Z cells. These results suggest that costunolide induces apoptosis in human endometriotic epithelial cells by inhibiting the prosurvival NFκB and Akt pathway, leading to the downregulation of anti-apoptotic protein Bcl-xL and XIAP and the activation of caspases.
著者
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PARK Hee-Juhn
Department of Botanical Resources, Sangji University
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Lee Kyung-tae
韓国
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Lee Kyung-tae
Coll. Of Pharmacy Kyung-hee Univerisity
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Lee Kyung-tae
Department Of Life And Nanopharmaceutical Sciences College Of Pharmacy Kyung Hee University
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Lee Kyung-tae
Department Of Biochemistry College Of Pharmacy Kyung Hee University
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Park Hee-juhn
Department Of Botanical Resources Sangi University
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Lee Kyung
College Of Pharmacy Kyung Hee University
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Lee Kyung-won
韓国
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Lee Kyung‐won
Kyung Hee Univ. Seoul Kor
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KIM Ji-Hyun
Department of Anatomy, Chonbuk National University Medical School
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Choi Jung-hye
Department Of Internal Medicine Hanyang University
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Kim Ji-hyun
Department Of Anatomy Chonbuk National University Medical School:research Center For Allergic Immune
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Yang Yeong-In
Department of Life & Nanopharamceutical Science, College of Pharmacy, Kyung Hee University
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Lee Kyung-Tae
Department of Life & Nanopharamceutical Science, College of Pharmacy, Kyung Hee University
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Choi Jung-Hye
Department of Life & Nanopharamceutical Science, College of Pharmacy, Kyung Hee University
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Yang Yeong-In
Department of Life & Nanopharamceutical Science, College of Pharmacy, Kyung Hee University
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