Hispolon inhibits breast cancer cell migration by reversal of epithelial-to-mesenchymal transition via suppressing the ROS/ERK/Slug/E-cadherin pathway

Abstract

Hispolon has been shown to have anticancer effects on various tumors. However, whether hispolon exerts anti-migration activity in breast cancer cells and the underlying mechanisms, have not been elucidated yet. In the present study, our data demonstrated that hispolon inhibited TPA-induced breast cancer MCF-7 cell migration at sub-toxic concentrations in vitro. Hispolon decreased the level of cellular ROS significantly and repressed TPA-induced phosphorylation of extracellular signal-regulated kinase (ERK), accompanied by upregulation of E-cadherin and downregulation of the transcriptional repressor Slug. Furthermore, N-acetyl-cysteine, an antioxidant agent, markedly suppressed TPA-induced epithelial-to-mesenchymal transition, cell migration and activation of ERK. Taken together, our results indicated that hispolon suppressed the migration of breast cancer cells via suppressing the ROS/ERK/Slug/E‑cadherin pathway. Hispolon may be developed as a potential antimetastasis agent to breast cancer.

Expression of EMT markers and mode of surgery are prognostic in phyllodes tumors of the breast

“…We also observed that increased E-cadherin, Snail, Slug and Twist expression was associated with the malignant phenotype of PTs. Our findings were concordant with previous studies that showed that EMT markers (E-cadherin, Snail, Slug and Twist) expression ( P =0.025, P =0.001, P <0.01, P =0.044, respectively) correlated more strongly with borderline and malignant PTs than with benign PT [25]. However, no significant difference in N-cadherin ( P =0.146) expression was observed between the malignant/borderline and the benign groups.…”

Hispolon: A natural polyphenol and emerging cancer killer by multiple cellular signaling pathways

“… Cancer type Cell line No. of cells/well Treatment time IC 50 Molecular targets Cell cycle arrest References Glioblastoma U87MG 1 × 10 4 24, 48, 72 h – Cyclin D4↓, p2↑, p53↑, CDK4↓, p-ERK 1↓1 G2/M Arcella et al (2017) Cervical HeLa, SiHa 7 × 10 4 24 h – p-AKT↓, ERK Act , LC3- II↑, MMP-2↓, MMP-9↓ – Hsin et al (2017) Breast MCF-7, T47D, MDA-MB-231 5 × 10 3 , 5 × 10 4 24 h 70 Mm ERα↓, PARP↑, Bcl-2↓, E-cadherin↓, MMP-9↓, p-IκBα┴, p- NF-κB↓ – ( Jang et al, 2015 ; Sun et al, 2015 ; Zhao et al, 2016 ; Wang et al, 2017 ) Naso-pharyngeal HONE-1, NPC-39, NPC-BM, NPC-039 5 × 10 4 – – p-Akt┴, uPA┴, MMP-2↓, MMP-9↓, caspase-3 Act , caspase-8 Act , caspase-9 Act – ( Hsieh et al, 2014 ; Ho et al, 2017 ) Lung A549, H661 1 × 10 4 24, 48, 72 h 35.9 ± 6.9, 28.8 ± 3.1, 8.1 ± 2.3 μM Cyclin D1↓, CDK2↓, CDK4↓, cyclin E↓, CDK6↓, p27↑, p21↑ G0/G1 …”

“…Metastasis is a primary cause of mortalities and most complicated obstacle in the development of effective cancer therapies ( Zhao et al, 2016 ). Metastasis is characterized by four important steps: detachment, migration and adhesion of cancer cells to secondary sites.…”

Involvement of Up-regulation of Death Receptors and Bim in Hispolon-mediated TNF-related Apoptosis-inducing Ligand Sensitization in Human Renal Carcinoma

“…Hispolon is an active phenol compound that is isolated from Phellinus linteus . It has various biological functions including anti–inflammatory, anti-oxidant, anti-proliferative, and anti-tumor effects [1–5]. Anti-tumor effect of hispolon has been shown through inhibition of cell growth, induction of cell cycle arrest and apoptosis, and inhibition of metastasis in various types of cancer [3,5–9].…”

“…Anti-tumor effect of hispolon has been shown through inhibition of cell growth, induction of cell cycle arrest and apoptosis, and inhibition of metastasis in various types of cancer [3,5–9]. Down-regulation of G1/S transition-related proteins [6,10], modulation of extracellular signal-regulated kinase phosphorylation [1], and reactive oxygen species-mediated mitochondria damage [9] were proposed to involvement in anti-cancer effect by hispolon. However, there have been no reports on the anti-tumor effects of hispolon in renal carcinoma cells.…”