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KMID : 0043320110340081323
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Archives of Pharmacal Research
2011 Volume.34 No. 8 p.1323 ~ p.1329
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1-oxoeudesm-11(13)-ene-12,8α-lactone-induced apoptosis via ROS generation and mitochondria activation in MCF-7 cells
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Cui Min
Zhang Yahong
Liu Shanshan
Xie Weidong
Ji Mei
Lou Hongxiang
Li Xia
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Abstract
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A novel eudesmane-type sesquiterpene compound, 1-oxoeudesm-11(13)-eno-12,8a-lactone (OEL), was isolated from Aster himalaicus. Its effect on apoptosis in human breast adenocarcinoma (MCF-7) cells was investigated. MTT assay showed that OEL substantially reduced the viability of KB, MCF-7, U87, A172, and MG-63 cells. MCF-7 cells were used to further evaluate the antitumor effects and anticancer mechanisms of OEL. OEL-induced apoptosis was characterized by chromatin condensation, formation of apoptotic bodies, and phosphatidylserine on extracellular surface; these effects were confirmed by DAPI nuclear staining and flow cytometry. Increased expression of Bax and deceased expression of Bcl-2 were also observed in OELtreated MCF-7 cells. Moreover, OEL induced the loss of mitochondria membrane potential, release of cytochrome C, activation of caspase-9, and generation of reactive oxygen species. These findings indicate that reactive oxygen species generation and mitochondria activation were involved in apoptosis induced by OEL in MCF-7 cells. The results from our study demonstrated that OEL may be a promising pro-apoptotic compound that could be used to develop novel anticancer drugs.
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KEYWORD
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Eudesmane, OEL, Aster himalaicus, Apoptosis, ROS, MCF-7
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