Actein Inhibits the Proliferation and Adhesion of Human Breast Cancer Cells and Suppresses Migration in vivo

Abstract

Background and purpose: Metastasis is an important cause of death in breast cancer patients. Anti-metastatic agents are urgently needed since standard chemotherapeutics cannot diminish the metastatic rate. Actein, a cycloartane triterpenoid, has been demonstrated to exhibit anti-angiogenic and anti-cancer activities. Its anti-metastatic activity and underlying mechanisms were evaluated in the present study.Methods: The effects of actein on the proliferation, cell cycle phase distribution, migration, motility and adhesion were evaluated using two human breast cancer cell lines, MDA-MB-231 (estrogen receptor-negative) and MCF-7 cells (estrogen receptor-positive) in vitro. Western blots and real-time PCR were employed to examine the protein and mRNA expression of relevant signaling pathways. A human metastatic breast cancer cell xenograft model was established in transparent zebrafish embryos to examine the anti-migration effect of actein in vivo.Results: In vitro results showed that actein treatment significantly decreased cell proliferation, migration and motility. Furthermore, actein significantly caused G1 phase cell cycle arrest and suppressed the protein expression of matrix metalloproteinases of MDA-MB-231 cells. In addition, actein inhibited breast cancer cell adhesion to collagen, also reduced the expression of integrins. Actein treatment down-regulated the protein expression of epidermal growth factor receptor (EGFR), AKT and NF-κB signaling proteins. In vivo results demonstrated that actein (60 μM) significantly decreased the number of zebrafish embryos with migrated cells by 74% and reduced the number of migrated cells in embryos.Conclusion: Actein exhibited anti-proliferative, anti-adhesion and anti-migration activities, with the underlying mechanisms involved the EGFR/AKT and NF-kappaB signalings. These findings shed light for the development of actein as novel anti-migration natural compound for advanced breast cancer.

TGFβ and Hippo Pathways Cooperate to Enhance Sarcomagenesis and Metastasis through the Hyaluronan-Mediated Motility Receptor (HMMR)

“…7C). We and others have performed similar studies using MDA-MB-231 breast cancer cells and other tumor cell types and have observed predominantly singlecell migration in MDA-MB-231 (48), whereas other tumor cell types cluster prior to extravasation (49). This clustering may be an important contributor to extravasation and metastatic outgrowth in sarcoma and will be investigated in future studies.…”

A systems pharmacology approach to determine the mechanisms of action of pleiotropic natural products in breast cancer from transcriptome data

“…Actein is a widely studied natural triterpene glycoside that has recently attracted attention in breast cancer due to its effects on various biological processes in cancer 16, 47–49 . In this study, cell death and cell cycle roles of TGF-beta, PI3K-Akt-mTOR and NRF2 pathways were up-regulated while proliferation roles of TGF-beta pathway were down-regulated.…”

“…Additionally, tumor microenvironment regulation through interferon signaling pathway was down-regulated ( Table 3 ). Available reports on breast and other cancers indicate that actein targets cell apoptosis 48, 50 , cell adhesion 49 and migration 49, 50 . This analysis showed actein to target oncogenic signalling pathways mainly regulating cell cycle, proliferation and apoptosis processes in this cell type.…”

Actein Inhibits Tumor Growth and Metastasis in HER2-Positive Breast Tumor Bearing Mice via Suppressing AKT/mTOR and Ras/Raf/MAPK Signaling Pathways

“…Actein ( Figure 1A) was extracted and isolated from roots of Cimicifuga foetida. The details of extraction and isolation procedures for actein have been reported previously (27). Actein (99% purity) in dry powder form was dissolved in dimethylsulfoxide (DMSO) at a concentration of 100 mM as the stock solution.…”

“…Actein exhibits the in vitro anti-proliferation and anti-migration effect in human non-small cell lung cancer cells (21) as well as osteosarcoma cells (25). For breast cancer, actein could inhibit the growth and proliferation of both mouse and human breast cancer cells (26,27). Moreover, our previous studies have demonstrated that actein exhibited anti-angiogenic and anti-metastatic activities in mouse 4T1 mammary breast tumor-bearing model (26), and also the migration inhibition effect on human breast cancer xenograft zebrafish model (27).…”