2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway

Context: Caragana pruinosa Kom. (Fabaceae), a commonly used folk medicine, has been found to possess antitumor effects. However, the antiproliferative effect of 2,4-dihydroxy-3′-methoxy-4′-ethoxychalcone (DMEC) derived from C. pruinosa against multiple myeloma (MM) has never been investigated. Objec...

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Autores principales:	FengChen Zhu, DianMing Jiang, MingHua Zhang, Bo Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	caragana pruinosa kom. u266 cleaved-caspase-3 cleaved-caspase-9 bcl-2 z-vad-fak igf-1 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/e2a1a17c74604e8bb0e4378e35e41f5f
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spelling	oai:doaj.org-article:e2a1a17c74604e8bb0e4378e35e41f5f2021-11-17T14:21:56Z2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway1388-02091744-511610.1080/13880209.2019.1662814https://doaj.org/article/e2a1a17c74604e8bb0e4378e35e41f5f2019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1662814https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Caragana pruinosa Kom. (Fabaceae), a commonly used folk medicine, has been found to possess antitumor effects. However, the antiproliferative effect of 2,4-dihydroxy-3′-methoxy-4′-ethoxychalcone (DMEC) derived from C. pruinosa against multiple myeloma (MM) has never been investigated. Objective: This study systematically evaluates the antiproliferative effect of DMEC against MM cells. Materials and methods: The antiproliferative effect of DMEC (1, 2, 4, 8, 16, 32, and 64 μM) on MM cells lines, including RPMI8226, MM.1S, and U266, was examined using Cell counting kit-8 (CCK-8) assay after 24 h incubation. The proapoptotic effect of DMEC (20 μM) was determined using fluorescent microscope and flow cytometer, and its possible underlying mechanisms were further studied by using western blotting analysis. Results: The half maximal inhibitory concentrations (IC50) of DMEC on RPMI8226, MM.1S, and U266 cells were calculated as 25.97, 18.36, and 15.02 μM, respectively. The inhibitory effect of DMEC on MM cells was related to mitochondria-mediated apoptosis via upregulation of the cleaved-caspase-3 (C-3), cleaved-caspase-9 (C-9), Bad, and cytochrome C (Cyto C), but downregulation of the Bcl-2 and poly ADP-ribose polymerase (PARP). Furthermore, DMEC (5, 10, and 20 μM) reduced the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylated (p)-protein kinase B (Akt), and p-mammalian target of rapamycin (p-mTOR), which were further evidenced by pretreatment with IGF-1, a PI3K activator. Conclusion: Collectively, our results indicate that the DMEC could be treated as a new candidate for treatment of multiple myeloma in the future. Also, an in vivo study is warranted in the future.FengChen ZhuDianMing JiangMingHua ZhangBo ZhaoTaylor & Francis Grouparticlecaragana pruinosa kom.u266cleaved-caspase-3cleaved-caspase-9bcl-2z-vad-fakigf-1Therapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 641-648 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	caragana pruinosa kom. u266 cleaved-caspase-3 cleaved-caspase-9 bcl-2 z-vad-fak igf-1 Therapeutics. Pharmacology RM1-950
spellingShingle	caragana pruinosa kom. u266 cleaved-caspase-3 cleaved-caspase-9 bcl-2 z-vad-fak igf-1 Therapeutics. Pharmacology RM1-950 FengChen Zhu DianMing Jiang MingHua Zhang Bo Zhao 2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway
description	Context: Caragana pruinosa Kom. (Fabaceae), a commonly used folk medicine, has been found to possess antitumor effects. However, the antiproliferative effect of 2,4-dihydroxy-3′-methoxy-4′-ethoxychalcone (DMEC) derived from C. pruinosa against multiple myeloma (MM) has never been investigated. Objective: This study systematically evaluates the antiproliferative effect of DMEC against MM cells. Materials and methods: The antiproliferative effect of DMEC (1, 2, 4, 8, 16, 32, and 64 μM) on MM cells lines, including RPMI8226, MM.1S, and U266, was examined using Cell counting kit-8 (CCK-8) assay after 24 h incubation. The proapoptotic effect of DMEC (20 μM) was determined using fluorescent microscope and flow cytometer, and its possible underlying mechanisms were further studied by using western blotting analysis. Results: The half maximal inhibitory concentrations (IC50) of DMEC on RPMI8226, MM.1S, and U266 cells were calculated as 25.97, 18.36, and 15.02 μM, respectively. The inhibitory effect of DMEC on MM cells was related to mitochondria-mediated apoptosis via upregulation of the cleaved-caspase-3 (C-3), cleaved-caspase-9 (C-9), Bad, and cytochrome C (Cyto C), but downregulation of the Bcl-2 and poly ADP-ribose polymerase (PARP). Furthermore, DMEC (5, 10, and 20 μM) reduced the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylated (p)-protein kinase B (Akt), and p-mammalian target of rapamycin (p-mTOR), which were further evidenced by pretreatment with IGF-1, a PI3K activator. Conclusion: Collectively, our results indicate that the DMEC could be treated as a new candidate for treatment of multiple myeloma in the future. Also, an in vivo study is warranted in the future.
format	article
author	FengChen Zhu DianMing Jiang MingHua Zhang Bo Zhao
author_facet	FengChen Zhu DianMing Jiang MingHua Zhang Bo Zhao
author_sort	FengChen Zhu
title	2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway
title_short	2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway
title_full	2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway
title_fullStr	2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway
title_full_unstemmed	2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway
title_sort	2,4-dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the pi3k/akt/mtor signaling pathway
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/e2a1a17c74604e8bb0e4378e35e41f5f
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2,4-Dihydroxy-3′-methoxy-4′-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway

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