Nm23-H1 activator phenylbutenoid dimer exerts cytotoxic effects on metastatic breast cancer cells by inducing mitochondrial dysfunction only under glucose starvation
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Kim, Bokyung; Lee, Jae-Jin; Suh, Ji-Wan; Lee, Kong-Joo] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Shin, Ji Soo; Lee, Hee-Yoon] Korea Adv Inst Sci & Technol, Dept Chem, Daejeon 34051, South Korea; [Jung, Sunhee; Hwang, Geum-Sook] Korea Basic Sci Inst, Western Seoul Ctr, Integrated Metabol Res Grp, Seoul 03759, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 NATURE PORTFOLIO
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190428
- 본문언어 영어
- Published As https://doi.org/10.1038/s41598-021-02729-7
- PubMed https://pubmed.ncbi.nlm.nih.gov/34876614
초록/요약
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.
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