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Tomentodione M sensitizes multidrug resistant cancer cells by decreasing P-glycoprotein via inhibition of p38 MAPK signaling

Oncotarget,. 2017; 
Zhou, X.-W., Xia, Y.-Z., Zhang, Y.-L., Luo, J.-G., Han, C., Zhang, H., … Kong, L.-Y.
Products/Services Used Details Operation
Gene Synthesis The pMT3 p38 plasmid was a gift from John Kyriakis (Addgene plasmid # 12658). The MDR1 plasmid was purchased from Genscript (Nanjing, China). The proteasome inhibitor SB203580 and SP600125 were purchased from MedChem Express (MCE, Shanghai, China). The primary antibodies for P-gp, p38, p-p38, p-JNK, p-ERK, PARP, cleaved-PARP, Caspase-9, cleavedCaspase-9, Caspase-3, cleaved-Caspase-3 and GAPDH were purchased from Cell Signaling Technology (CST, Danvers, MA). Goat anti-rabbit and goat anti-rabbit IgG Fab2 Alexa Fluor (R) antibodies (CST) were used as secondary antibodies. TTM was reserved in DMSO at the concentration of 50 mM. CCK-8 solution was purchased from qcbio Science & Technologies (Shanghai, China) Get A Quote

摘要

In this study, we investigated the mechanism by which tomentodione M (TTM), a novel natural syncarpic acid-conjugated monoterpene, reversed multi-drug resistance (MDR) in cancer cells. TTM increased the cytotoxicity of chemotherapeutic drugs such as docetaxel and doxorubicin in MCF-7/MDR and K562/MDR cells in a dose- and time-dependent manner. TTM reduced colony formation and enhanced apoptosis in docetaxel-treated MCF-7/MDR and K562/MDR cells, and it enhanced intracellular accumulation of doxorubicin and rhodamine 123 in MDR cancer cells by reducing drug efflux mediated by P-gp. TTM decreased expression of both P-gp mRNA and protein by inhibiting p38 MAPK signaling. Similarly, the p38 MAPK inhibitor SB203580 r... More

关键词

: tomentodione M; meroterpenoid; multidrug resistance; P-glycoprotein; p38