Furanodiene alters mitochondrial function in doxorubicin-resistant MCF-7 human breast cancer cells in an AMPK-dependent manner

doi:10.1039/c6mb00003g

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	Furanodiene alters mitochondrial function in doxorubicin-resistant MCF-7 human breast cancer cells in an AMPK-dependent manner
	Zhong, ZF; Tan, W; Qiang, WW; Scofield, VL; Tian, K; Wang, CM; Qiang, WA; Wang, YT; Wang, YT (reprint author), Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Ave Univ, Taipa 999078, Peoples R China.; Qiang, WA (reprint author), Northwestern Univ, Div Reprod Sci Med, Dept Obstet & Gynecol, Feinberg Sch Med, 303 East Super St,Lurie 7-250, Chicago, IL 60611 USA.
刊名	MOLECULAR BIOSYSTEMS
	2016
卷号	12 期号:5 页码:1626-1637
ISSN号	1742-206X
DOI	10.1039/c6mb00003g
文献子类	Article
英文摘要	Furanodiene is a bioactive sesquiterpene isolated from the spice-producing Curcuma wenyujin plant (Y. H. Chen and C. Ling) (C. wenyujin), which is a commonly prescribed herb used in clinical cancer therapy by modern practitioners of traditional Chinese medicine. Previously, we have shown that furanodiene inhibits breast cancer cell growth both in vitro and in vivo, however, the mechanism for this effect is not yet known. In this study, therefore, we asked (1) whether cultured breast cancer cells made resistant to the chemotherapeutic agent doxorubicin (DOX) via serial selection protocols are susceptible to furanodiene's anticancer effect, and (2) whether AMP-activated protein kinase (AMPK), which is a regulator of cellular energy homeostasis in eukaryotic cells, participates in this effect. We show here (1) that doxorubicin-resistant MCF-7 (MCF-7/DOXR) cells treated with furanodiene exhibit altered mitochondrial function and reduced levels of ATP, resulting in apoptotic cell death, and (2) that AMPK is central to this effect. In these cells, furanodiene (as opposed to doxorubicin) noticeably affects the phosphorylation of AMPK and AMPK pathway intermediates, ACLY and GSK-3b, suggesting that furanodiene reduces mitochondrial function and cellular ATP levels by way of AMPK activation. Finally, we find that the cell permeable agent and AMPK inhibitor compound C (CC), abolishes furanodiene-induced anticancer activity in these MCF-7/DOXR cells, with regard to cell growth inhibition and AMPK activation; in contrast, AICAR (5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside, acadesine), an AMPK activator, augments furanodiene-induced anticancer activity. Furthermore, specific knockdown of AMPK in MCF-7/DOXR cells protects these cells from furanodiene-induced cell death. Taken together, these findings suggest that AMPK and its pathway intermediates are promising therapeutic targets for treating chemoresistant breast cancer, and that furanodiene may be an important chemical agent incorporated in next-generation chemotherapy protocols.
学科主题	Biochemistry & Molecular Biology
出版地	CAMBRIDGE
项目编号	Macao Science and Technology Development Fund [077/2011/A3, 048/2013/A2] ; Research Fund of University of Macau [CPG2014-00012-ICMS, UL016/09Y4/CMS/WYT01/ICMS, MYRG208 (Y3-L4)-ICMS11-WYT] ; Baskes Foundation ; Robert H. Lurie Comprehensive Cancer Center at Northwestern University
语种	英语
WOS记录号	WOS:000374936700020
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/179531]
专题	药学院_期刊论文
通讯作者	Wang, YT (reprint author), Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Ave Univ, Taipa 999078, Peoples R China.; Qiang, WA (reprint author), Northwestern Univ, Div Reprod Sci Med, Dept Obstet & Gynecol, Feinberg Sch Med, 303 East Super St,Lurie 7-250, Chicago, IL 60611 USA.
推荐引用方式 GB/T 7714	Zhong, ZF,Tan, W,Qiang, WW,et al. Furanodiene alters mitochondrial function in doxorubicin-resistant MCF-7 human breast cancer cells in an AMPK-dependent manner[J]. MOLECULAR BIOSYSTEMS,2016,12(5):1626-1637.
APA	Zhong, ZF.,Tan, W.,Qiang, WW.,Scofield, VL.,Tian, K.,...&Qiang, WA .(2016).Furanodiene alters mitochondrial function in doxorubicin-resistant MCF-7 human breast cancer cells in an AMPK-dependent manner.MOLECULAR BIOSYSTEMS,12(5),1626-1637.
MLA	Zhong, ZF,et al."Furanodiene alters mitochondrial function in doxorubicin-resistant MCF-7 human breast cancer cells in an AMPK-dependent manner".MOLECULAR BIOSYSTEMS 12.5(2016):1626-1637.