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Furanodiene alters mitochondrial function in doxorubicin-resistant MCF-7 human breast cancer cells in an AMPK-dependent manner
Zhong Z.-F.1; Tan W.2; Qiang W.W.1,3; Scofield V.L.4; Tian K.5,6; Wang C.-M.1; Qiang W.-A.6; Wang Y.-T.1
2016
Source PublicationMolecular BioSystems
Volume12Issue:5Pages:1626
Abstract

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-3β, 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-β-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. © 2016 The Royal Society of Chemistry.

KeywordAtp-citrate Lyase Activated Protein-kinase Double-strand Breaks In-vitro Multidrug-resistance Drug-resistance Metabolic-disorders Signaling Pathway Cellular-energy Natural-product
DOI10.1039/c6mb00003g
URLView the original
Indexed BySCIE
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000374936700020
The Source to ArticleScopus
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Cited Times [WOS]:16   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorQiang W.-A.; Wang Y.-T.
Affiliation1.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, 999078, Macau
2.School of Pharmacy, Lanzhou University, Lanzhou, Gansu province, 730000, China
3.Yale University, New Haven, CT 06511, United States
4.Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78541, United States
5.School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, 999077, Hong Kong
6.Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, 303 East Superior Street Lurie 7-250, Chicago, IL 60611, United States
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhong Z.-F.,Tan W.,Qiang W.W.,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.
APA Zhong Z.-F.,Tan W.,Qiang W.W.,Scofield V.L.,Tian K.,Wang C.-M.,Qiang W.-A.,&Wang Y.-T..(2016).Furanodiene alters mitochondrial function in doxorubicin-resistant MCF-7 human breast cancer cells in an AMPK-dependent manner.Molecular BioSystems,12(5),1626.
MLA Zhong Z.-F.,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.
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