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

ABSTRACT: 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-hydroxy2-hydroxymethyl)-2‑methyl propanoate (MTH‑3), and previous studies showed 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 examined using various assays and gelatin zymography, and western blot analysis. 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. The potential signaling pathways were revealed by next‑generation sequencing analysis, antibody microarray analysis and western blot analysis. In conclusion, the results of the present study show that, MTH‑3 inhibited 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 on TNBC.

SUBMITTER: Chiu YJ

PROVIDER: S-EPMC8144931 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

Chiu Yu-Jen YJ Tsai Fuu-Jen FJ Bau Da-Tian DT Chang Ling-Chu LC Hsieh Min-Tsang MT Lu Chi-Cheng CC Kuo Sheng-Chu SC Yang Jai-Sing JS

Oncology reports 20210520 1

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-hydroxy2-hydroxymethyl)-2‑methyl propanoate (MTH‑3), and previous studies showed that MTH‑3 inhibits TNBC proliferation and induces apoptosis <i>in vitro</i> and <i>in vivo</i> with a superior bioavailability and absorption than curcumin. In the pr ...[more]

PMID: 34013378

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Project description:Vasculogenic mimicry (VM) with the pattern of endothelial independent tubular structure formation lined by aggressive tumor cells mimics regular tumor blood vessels to ensure robust blood supply and correlates with the proliferation, invasion, metastasis, and poor prognosis of malignant tumors, which was demonstrated to be a major obstacle for resistance to antiangiogenesis therapy. Therefore, it is urgent to discover methods to abrogate the VM formation of tumors, which possesses important practical significance for improving tumor therapy. Brucine is a traditional medicinal herb extracted from seeds of Strychnos nux-vomica L. (Loganiaceae) exhibiting antitumor activity in a variety of cancer models. In the present study, the effect of brucine on vasculogenic mimicry and the related mechanism are to be investigated. We demonstrated that, in a triple-negative breast cancer cell line MDA-MB-231, brucine induced a dose-dependent inhibitory effect on cell proliferation along with apoptosis induction at higher concentrations. The further study showed that brucine inhibited cell migration and invasion with a dose-dependent manner. Our results for the first time indicated that brucine could disrupt F-actin cytoskeleton and microtubule structure, thereby impairing hallmarks of aggressive tumors, like migration, invasion, and holding a possibility of suppressing vasculogenic mimicry. Hence, the inhibitory effect of brucine on vasculogenic mimicry was further verified. The results illustrated that brucine significantly suppressed vasculogenic mimicry tube formation with a dose-dependent effect indicated by the change of the number of tubules, intersections, and mean length of tubules. The in-depth molecular mechanism of vasculogenic mimicry suppression induced by brucine was finally suggested. It was demonstrated that brucine inhibited vasculogenic mimicry which might be through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2 and matrix metalloproteinase-2 and metalloproteinase-9.

Dataset Information

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

Publications

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

Similar Datasets

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