%0 Journal Article
%T 2,4-Dihydroxy-3¡ä-methoxy-4¡ä-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myeloma via the PI3K/akt/mTOR signaling pathway
%A Bo Zhao
%A DianMing Jiang
%A FengChen Zhu
%A MingHua Zhang
%J Pharmaceutical Biology
%D 2019
%R https://doi.org/10.1080/13880209.2019.1662814
%X Abstract 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¡ä-methoxy-4¡ä-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£¿¦ÌM) 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£¿¦ÌM) 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£¿¦ÌM, 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£¿¦ÌM) 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
%U https://www.tandfonline.com/doi/full/10.1080/13880209.2019.1662814