The inhibitory effects of butein on cell proliferation and TNF-α-induced CCL2 release in racially different triple negative breast cancer cells.

Patricia Mendonca,Karam F. A. Soliman,David Bauer,Samia Messeha,Ainsley Horton,Salvatore V Pizzo

doi:10.1371/journal.pone.0215269

Patricia Mendonca, Karam F. A. Soliman + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0215269

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Journal: PloS one	Publication Date: Oct 30, 2019
Citations: 15	License type: CC BY 4.0

Affiliation: Florida Agricultural and Mechanical University

Abstract

Drug resistance is the leading cause of breast cancer-related mortality in women, and triple negative breast cancer (TNBC) is the most aggressive subtype, affecting African American women more aggressively compared to Caucasians women. Of all cancer-related deaths, 15 to 20% are associated with inflammation, where proinflammatory cytokines have been implicated in the tumorigenesis process. The current study investigated the effects of the polyphenolic compound butein (2′,3,4,4′-tetrahydroxychalcone) on cell proliferation and survival, as well as its modulatory effect on the release of proinflammatory cytokines in MDA-MB-231 (Caucasian) and MDA-MB-468 (African American) TNBC cell. The results obtained showed that butein decreased cell viability in a time and dose-dependent manner, and after 72-h of treatment, the cell proliferation rate was reduced in both cell lines. In addition, butein was found to have higher potency in MDA-MB-468, exhibiting anti-proliferative effects in lower concentrations. Apoptosis assays demonstrated that butein (50 μM) increased apoptotic cells in MDA MB-468, showing 60% of the analyzed cells in the apoptotic phase, compared to 20% in MDA-MB-231 cells. Additionally, butein downregulated both protein and mRNA expression of the proinflammatory cytokine, CCL2, and IKBKE in TNFα-activated Caucasian cells, but not in African Americans. This study demonstrates butein potential in cancer cell suppression showing a higher cytotoxic, anti-proliferative, and apoptotic effects in African Americans, compared to Caucasians TNBC cells. It also reveals the butein inhibitory effect on CCL2 expression with a possible association with IKBKE downregulation in MDA-MB-231 cells only, indicating that Caucasians and African Americans TNBC cells respond differently to butein treatment. The obtained findings may provide an explanation regarding the poor therapeutic response in African American patients with advanced TNBC.

Highlights

The increasing drug resistance in breast cancer therapy is the leading cause of cancer-related mortality in women [1]
Butein effect on breast cancer cell viability was investigated in MDA-MB-231 and MDA-MB468 cell lines after 24 h-treatment
The results indicate that butein effects on the two cell lines are different, causing higher cytotoxicity effect in MDA-MB-468 cells (Fig 1A)

Summary

Introduction

The increasing drug resistance in breast cancer therapy is the leading cause of cancer-related mortality in women [1]. Butein and TNBC invasive breast cancer to be diagnosed in the U.S, alongside 64,000 new cases of non-invasive breast cancer [2]. Breast cancer is classified into three major therapeutic subtypes: estrogen and/or progesterone receptor-positive (ER+, PR+), HER2+, and triple-negative breast cancer (TNBC) (lacking expression of ER, PR, and HER2) [3,4]. TNBC covers 15 to 20% of all breast cancers [5]. TNBC subtypes respond differently to the treatment, challenging, even more, the development of target therapy with certain chemotherapeutics that may be safe and effective at the same time [4,10]

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