Abstract
Simple SummaryCancer stem cells (CSCs) are responsible for tumour initiation, chemo- and radiotherapy resistance and cancer recurrence. CSCs display plasticity that enables them to alter their phenotype and function making them challenging to eliminate. In this study we explore the effects of an antiretroviral medication used to treat HIV/AIDS (Efavirenz) on cancer stem cells derived from multiple breast cancer cell lines. Efavirenz has been previously found to be effective in the treatment of triple-negative breast cancers, and here we show that it is also capable of altering CSC numbers, cell morphology, RNA/microRNA gene expression and levels of epithelial/mesenchymal CSC subtypes. This study shows that, with Efavirenz, it is possible to not only eliminate primary breast cancer cells, but also to promote changes in cell morphology.Although many breast cancer therapies show initial success in the treatment of the primary tumour, they often fail to eliminate a sub-population of cells known as cancer stem cells (CSCs). These cells are recognised for their self-renewal properties and for their capacity for differentiation often leading to chemo/radio-resistance. The antiviral drug Efavirenz has been shown to be effective in eliminating triple-negative breast cancer cells, and here we examine its effect on breast CSCs. The effects of Efavirenz on CSCs for several breast cancer cell lines were investigated by examining cellular changes upon drug treatment, including CSC numbers, morphology, RNA/microRNA expression and levels of epithelial/mesenchymal CSC subtypes. Efavirenz treatment resulted in a decrease in the size and number of tumorspheres and a reduction in epithelial-type CSC levels, but an increase in mesenchymal-type CSCs. Efavirenz caused upregulation of several CSC-related genes as well as miR-21, a CSC marker and miR-182, a CSC suppressor gene. We conclude that Efavirenz alters the phenotype and expression of key genes in breast CSCs, which has important potential therapeutic implications.
Highlights
Introductioncancer stem cells (CSCs) make up only a relatively small proportion of cancer cells and similar to other stem cells, possess stem-like characteristics [4]
Changes in Cancer Stem Cell Regulators/Indicators Observed in Efavirenz-Treated Breast
The use of Efavirenz as a potential cancer treatment for triple-negative breast cancers was previously explored by our group in various breast cancer cell lines [22]
Summary
CSCs make up only a relatively small proportion of cancer cells and similar to other stem cells, possess stem-like characteristics [4]. They are known as cancer-initiating cells because they can readily generate tumours when injected into immunodeficient mice [5]. Studies have shown that many cancer drugs can effectively eliminate cancer cells, the presence of CSCs will often lead to cancer metastasis and drug resistance, and their survival is responsible for tumour recurrence [1,7]
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