Next-generation sequencing analysis reveals that MTH-3, a novel curcuminoid derivative, suppresses the invasion of MDA-MB-231 triple-negative breast adenocarcinoma cells. MTH-3 SUPPRESSES BREAST CANCER INVASION

Triple-negative breast cancer (TNBC) behaves aggressively in the invasive and metastatic states. Our research group recently developed a novel curcumin derivative, (1E,3Z,6E)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl)bis(2-methoxy-4,1-phenylene)bis(3-hydroxy-2-hydroxymethyl)-2-methyl propanoate (MTH-3), and our previous studies have shown that MTH-3 inhibits TNBC proliferation and induces apoptosis in vitro and in vivo with a superior bioavailability and absorption than curcumin. In the present study, the effects of MTH-3 on TNBC cell invasion were explored. Treatment with MTH-3 inhibited MDA-MB-231 cell invasion and migration, as shown by Transwell assay, 3D spheroid invasion assay, and wound healing assay. The results of the gelatin zymography experiments revealed that MTH-3 decreased matrix metalloproteinase‐9 activity. Finally, the potential signaling pathways were revealed by next-generation sequencing analysis, antibody microarray analysis and western blotting. In conclusion, MTH-3 inhibits tumor cell invasion through the MAPK/ERK/AKT signaling pathway and cell cycle regulatory cascade, providing significant information about the potential molecular mechanisms of the effects of MTH-3 effects on TNBC.