Abstract

Up to 30% of breast cancer mortality is caused by cancer relapse despite primary clinical treatments due to distant metastases. Further research focusing on breast cancer mechanisms are needed for deeper understanding of disease prognosis. 3-bromopyruvate (3-BP), a glycolysis inhibitor, has been studied as one of the antitumor agents in recent years. In this report, we want to investigate the form of cell death induced by 3-BP and demonstrate the inhibitory effect of 3-BP on breast cancer cell proliferation and its mechanism in vivo and in vitro. We found that 3-BP could inhibit MDA-MB-231 and MCF-7 breast cancer cell proliferation, through energy metabolism inhibition. Further, necroptosis characters in MDA-MB-231 cells after 3-BP treatment were observed, which could be negatively regulated through Ppm1b by dephosphorylation of RIP3. In addition, 3-BP treatment in an MDA-MB-231 cell-transplanted mouse model showed a significant antitumor effect, which correlated with necroptosis-related protein Ppm1b. The findings demonstrate the potential for 3-BP in the treatment of breast cancer, providing impetus for further clinical studies.

Highlights

  • Breast cancer is one of the dominant types of cancers, which affects public health, especially in Molecular and Cellular Oncology, women [1, 2]

  • We report the cell death forms induced by 3-BP, we found that 3-BP, a glycolysis inhibitor can induce cell death in breast cancer cells, MDA-MB-231 and MCF-7, respectively, especially in MDA-MB-231 cells by regulating Ppm1b and necroptosis, which are crucial for our understanding of breast cancer cell death signaling network

  • MDA-MB-231 cells for 240 min, and MCF-7 cells are mainly Cellular necroptosis is a necrotic programmed cell death dominated by cell body shrinkage, which proves that 3-BP modality pathway in a caspase-independent fashion and is induced necrotic apoptosis in MDA-MB-231 cells and 3-BP mainly mediated by RIP1 [14] and RIP3 [15]

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Summary

Introduction

Breast cancer is one of the dominant types of cancers, which affects public health, especially in Molecular and Cellular Oncology, women [1, 2]. Up to 30% of the patients die due to distant metastatic a section of the journal formation [3], and patients with metastatic breast cancer survive no more than 1 year [4]. Frontiers in Oncology various strategies need to be explored to understand mechanisms involved in breast cancer and to Received: 25 April 2020 provide better clinical treatment. 3-BP is a small reactive molecule formed by bromination of pyruvate, which is one of the widely studied compounds due to its antitumor properties [5].

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