Arrabidaea chica chloroform extract modulates estrogen and androgen receptors on luminal breast cancer cells

Douglas C Brandão,Joyce F C Guerra,Carina S Cordeiro,Matheus C Gazolla,Isabella C Martins,Paula M A P Lima,Antonielle O Cordeiro,Priscila C Orsolin,Ademar A Da Silva Filho,Thaise G Araújo,Danilo S Costa,Lara Vecchi

doi:10.1186/s12906-022-03506-3

Abstract

BackgroundBreast Cancer (BC) is the most common cancer in women worldwide and, although 70% of patients are responsive to selective Estrogen Receptor (ER) modulators such as Tamoxifen (Tam), patients’ survival is comprised by resistance to endocrine therapy. Brazilian flora, especially the Amazon biome, is one of the richest global sources of native species with potentially bioactive compounds. Arrabidaea chica is a plant native to the Amazon that has been used in the treatment of different diseases. However, its action on BC remains unclear.MethodsHerein the biological effects of the chloroform extract of A. chica (CEAC) were evaluated on BC cells and in in vivo model. After confirmation of CEAC antioxidant capacity, cells were treated with CEAC and Tam, alone and with CEAC+Tam. The cell viability was evaluated by MTT and hormone receptor transcripts levels were assessed (ESR1, ESR2 and AR). Finally, anticarcinogenicity of CEAC was recorded in Drosophila melanogaster through Epithelial Tumor Test (ETT).ResultsThe study confirmed the antioxidant activity of CEAC. CEAC was selective for MCF-7, downregulating ESR2 and AR transcripts and upregulating ESR2 expression. The modulatory effects of CEAC on ERs did not differ between cells treated with Tam and with CEAC+Tam. Interestingly, previous treatment with CEAC, followed by treatment with Tam promoted a significant decrease in cell viability. The extract also presented anticarcinogenic effect in in vivo assay.ConclusionThe bioassays on breast tumor cells demonstrated the antiproliferative activity of the extract, which modulated the expression of hormone receptors and sensitized luminal tumor cells to Tam. These results suggest that CEAC could be a complementary treatment for BC.

Highlights

Breast Cancer (BC) is the most common cancer in women worldwide and, 70% of patients are responsive to selective Estrogen Receptor (ER) modulators such as Tamoxifen (Tam), patients’ survival is comprised by resistance to endocrine therapy
Antioxidant potential and cytotoxicity The antioxidant potential of chloroform extract of A. chica (CEAC) was determined by the radical scavenging activity using the ABTS+ method and the results expressed as % of inhibition relative to Trolox as reference standard
The cytotoxicity of CEAC was significantly higher for MCF-7 cells when compared to control and to other cell lines, mainly in concentrations above 62 μg/ mL

Summary

Introduction

Breast Cancer (BC) is the most common cancer in women worldwide and, 70% of patients are responsive to selective Estrogen Receptor (ER) modulators such as Tamoxifen (Tam), patients’ survival is comprised by resistance to endocrine therapy. Breast cancer (BC) remains the most common non cutaneous tumor among women worldwide [3,4,5]. Nuclear receptor (NR) family of transcription factors plays essential roles in development and maintenance of malignant breast cells [11]. Estrogen receptor (ER) and Androgen receptor (AR) are frequently co-expressed in BC, they may behave in different ways in view of the tumor heterogeneity [12]. ER-α and ER-β have similar binding affinities for estrogens; share a high degree of homology in the DNA-binding regions but interact with different other proteins suggesting divergence in transcriptional machinery control [13]. AR is structurally similar to ERs and how it drives, promotes or controls breast tumorigenesis remains largely unexplored [15, 16]

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