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Nm23-H1 activator phenylbutenoid dimer exerts cytotoxic effects on metastatic breast cancer cells by inducing mitochondrial dysfunction only under glucose starvation

Title
Nm23-H1 activator phenylbutenoid dimer exerts cytotoxic effects on metastatic breast cancer cells by inducing mitochondrial dysfunction only under glucose starvation
Authors
Kim, BokyungLee, Jae-JinShin, Ji SooSuh, Ji-WanJung, SunheeHwang, Geum-SookLee, Hee-YoonLee, Kong-Joo
Ewha Authors
이공주
SCOPUS Author ID
이공주scopusscopus
Issue Date
2021
Journal Title
SCIENTIFIC REPORTS
ISSN
2045-2322JCR Link
Citation
SCIENTIFIC REPORTS vol. 11, no. 1
Publisher
NATURE PORTFOLIO
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Mitochondrial oxidative phosphorylation (OXPHOS) has become an attractive target in anti-cancer studies in recent years. In this study, we found that a small molecule phenylbutenoid dimer NMac1 (Nm23-H1 activator 1), (+/-)-trans-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene, a previously identified anti-metastatic agent, has novel anti-proliferative effect only under glucose starvation in metastatic breast cancer cells. NMac1 causes significant activation of AMPK by decreasing ATP synthesis, lowers mitochondrial membrane potential (MMP, Delta psi m), and inhibits oxygen consumption rate (OCR) under glucose starvation. These effects of NMac1 are provoked by a consequence of OXPHOS complex I inhibition. Through the structure-activity relationship (SAR) study of NMac1 derivatives, NMac24 was identified as the most effective compound in anti-proliferation. NMac1 and NMac24 effectively suppress cancer cell proliferation in 3D-spheroid in vivo-like models only under glucose starvation. These results suggest that NMac1 and NMac24 have the potential as anti-cancer agents having cytotoxic effects selectively in glucose restricted cells.
DOI
10.1038/s41598-021-02729-7
Appears in Collections:
약학대학 > 약학과 > Journal papers
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