Mechanical Changes and Microfilament Reorganization Involved in Microcystin-LR-Promoted Cell Invasion in DU145 and WPMY Cells.

Qiang Zhang,Zhifang Pan,Zumu Liang,Zhiqin Gao,Yongfang Xie,Weiguo Feng,Guohui Wang,Guihua Wang

doi:10.3389/fphar.2020.00089

Abstract

Microcystin-leucine arginine (MC-LR) is a potent tumor initiator that can induce malignant cell transformation. Cellular mechanical characteristics are pivotal parameters that are closely related to cell invasion. The aim of this study is to determine the effect of MC-LR on mechanical parameters, microfilament, and cell invasion in DU145 and WPMY cells. Firstly, 10 μM MC-LR was selected as the appropriate concentration via cell viability assay. Subsequently, after MC-LR treatment, the cellular deformability and viscoelastic parameters were tested using the micropipette aspiration technique. The results showed that MC-LR increased the cellular deformability, reduced the cellular viscoelastic parameter values, and caused the cells to become softer. Furthermore, microfilament and microfilament-associated proteins were examined by immunofluorescence and Western blot, respectively. Our results showed that MC-LR induced microfilament reorganization and increased the expression of p-VASP and p-ezrin. Finally, the impact of MC-LR on cell invasion was evaluated. The results revealed that MC-LR promoted cell invasion. Taken together, our results suggested that mechanical changes and microfilament reorganization were involved in MC-LR-promoted cell invasion in DU145 and WPMY cells. Our data provide novel information to explain the toxicological mechanism of MC-LR.

Highlights

Microcystins (MCs) are a group of cyclic heptapeptide toxins produced by freshwater cyanobacteria (Rastogi et al, 2014), among which microcystin-leucine arginine (MC-LR) is the most abundant and toxic congener (Li Y. et al, 2016)
We investigated the influence of Microcystin-leucine arginine (MC-LR) on mechanical parameters, microfilament, and cell invasion in DU145 and WPMY cells
Our results suggested that mechanical changes and microfilament reorganization were involved in MC-LR-promoted cell invasion in DU145 and WPMY cells

Summary

Introduction

Microcystins (MCs) are a group of cyclic heptapeptide toxins produced by freshwater cyanobacteria (Rastogi et al, 2014), among which microcystin-leucine arginine (MC-LR) is the most abundant and toxic congener (Li Y. et al, 2016). MC-LR can induce oxidative stress by increasing the reactive oxygen species (ROS) or decreasing the glutathione (GSH). Oxidative stress caused by MC-LR might induce mitochondrial permeability transition and apoptosis (Ma et al, 2016; Ma et al, 2018; Wu et al, 2019). Previous studies indicated that MC-LR is a potent tumor initiator (Zhao et al, 2016; Zhu et al, 2018), which could induce malignant cell transformation. Liu et al reported that MC-LR promoted proliferation and inhibited apoptosis in normal human liver cells (HL7702) (Liu et al, 2016). The study of Wang et al showed that MC-LR induced cytoskeleton reorganization, resulting in increased cell migration in human laryngeal epithelial cells (Hep-2) (Wang et al, 2017). The effect of MC-LR on prostate cancer (PCa) cells and normal prostate cells has yet been studied

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