Chloroquine (CQ) exerts anti-breast cancer through modulating microenvironment and inducing apoptosis

Int Immunopharmacol. 2017 Jan:42:100-107. doi: 10.1016/j.intimp.2016.11.027. Epub 2016 Nov 29.

Abstract

CQ is an anti-malaria drug, which has been used for years. However, there are published articles about its activity in anti-cancers. The aim of this approach was to look at possibility and related mechanisms of anti-breast cancer (mouse breast cancer cell line 4T1) by CQ alone. The studies of anti 4T1 in vitro and in vivo by CQ were performed. The growth of 4T1 in vitro and in vivo, survival of mice post treatment with CQ, changes of immune parameters and microenvironment in mice were evaluated. Our results demonstrate that CQ could markedly inhibit growth of 4T1 in vitro through inducing apoptosis of cells, inhibiting secretion of TGF-β and prolong the mice survival in vivo through boosting immune system by upregulating CD8+ T cell, and through down-regulating tumor associated macrophages (TAM), myeloid derived suppressing cells (MDSC) and Tregs, in microenvironment of mice bearing tumor. This provides a new mode of action for CQ and it is therefore concluded that CQ could be with potential in breast cancer therapy.

Keywords: Breast cancer; Chloroquine; Immunoregulation; Tumor microenvironment.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cellular Microenvironment / drug effects
  • Chloroquine / therapeutic use*
  • Female
  • Humans
  • Lymphocyte Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred BALB C
  • Myeloid-Derived Suppressor Cells / drug effects*
  • Myeloid-Derived Suppressor Cells / immunology
  • Neoplasm Transplantation
  • Transforming Growth Factor beta / metabolism*
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Transforming Growth Factor beta
  • Chloroquine