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Jaceosidin induces apoptosis in ras-transformed human breast epithelial cells through generation of reactive oxygen species

Cited 36 time in Web of Science Cited 34 time in Scopus
Authors
Kim, Min-Jung; Kim, Do-Hee; Lee, Ki Won; Yoon, Do-Young; Surh, Young-Joon
Issue Date
2007-03
Citation
Annals of the New York Academy of Sciences, Vol.1095, pp.483-495
Keywords
jaceosidineupatilinMCF10A-ras cellsROSapoptosisERKAkt
Abstract
Extracts of Artemisia plants possess anti-inflammatory and antioxidative activities. Eupatilin (5,7-dihydroxy-3',4',6-tri-methoxynavone), a pharmacologically active flavone derived from Artemisia asiatica, was shown to inhibit phorbol ester-induced cyclooxygenase-2 expression and NF-kappa B activation in mouse skin, and also to induce cell cycle arrest in ras-transformed human mammary epithelial (MCF10A-ras) cells. In this article, we examined the ability of jaceosidin (4',5,7-trihydroxy-3',6-dimethoxyflavone) isolated from Artemisia argyi to inhibit the proliferation of MCF10A-ras cells. Jaceosidin reduced the viability of MCF10A-ras cells to a greater extent than eupatilin. Jaceosidin treatment resulted in increased intracellular accumulation of reactive oxygen species (ROS) in MCF10A-ras cells, which was blocked by the antioxidant N-acetylcysteine (NAC). NAC attenuated jaceosidin-induced cytotoxicity. To better assess the proapoptotic effects of jaceosidin, we analyzed the treated cells by the flow cytometry. MCF10A-ras cells treated with jaceosidin (100 mu M) exhibited the increased proportion of hypodiploid or apoptotic cells (48.72% as composed to 7.78% in control cells). Jaceosidin treatment also increased the ratio of proapoptotic Bax to the antiapoptotic Bcl-2 and induced the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP). Moreover, jaceosidin elevated the expression of p53 and p21, while the compound inhibited the activation of ERK1/2 that is an important component of cell survival signaling.
ISSN
0077-8923
URI
https://hdl.handle.net/10371/172760
DOI
https://doi.org/10.1196/annals.1397.052
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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