Ethanolic Extracts from Azadirachta indica Leaves Modulate Transcriptional Levels of Hormone Receptor Variant in Breast Cancer Cell Lines

Abstract

Breast Cancer (BC) encompasses numerous entities with different biological and behavioral characteristics, favored by tumor molecular complexity. Azadirachta indica (neem) presents phenolic compounds, indicating its potential as an antineoplastic compound. The present study aimed to evaluate the cellular response of MCF10, MCF7, and MDA-MB-231 breast cell lines to ethanolic extracts of neem leaves (EENL) obtained by dichloromethane (DCM) and ethyl acetate (EA) solvent. Extracts’ antiproliferative activities were evaluated against MCF 10A, MCF7, and MDA-MB-231 for 24 and 48 h using MTT assay. ESR1, ESR2, AR, AR-V1, AR-V4, and AR-V7 transcripts were quantified through qPCR for 0.03125 μg/mL of DCM and 1.0 μg/mL for EA for 48 h. The EENL was tested on Drosophila melanogaster as a sole treatment and then also together with doxorubicin. Antiproliferative effect on tumor cell lines without affecting MCF 10A were 1.0 µg/mL (P < 0.001) for EA, and 0.03125 µg/mL (P < 0.0001) for DCM, both after 48 h. Transcriptional levels of AR-V7 increased after treatment. In vivo assays demonstrated that EENL induced fewer tumors at a higher concentration with doxorubicin (DXR). The behavior of AR-V7 in the MDA-MB-231 tumor lineage indicates new pathways involved in tumor biology and this may have therapeutic value for cancer.

Avaliação do efeito carcinogênico do bromazepam em Drosophila melanogaster

“…Para controle negativo foi utilizada água ultrapura, evidenciando uma frequência de 0,29 tumor/mosca, em um total de 200 moscas analisadas. Essa discreta indução tumoral ocorre devido à predisposição genética intrínseca do organismo teste e a ocorrência aleatória/espontânea de alterações genéticas (ALVES; BRAGA et al, 2018). Por outro lado, as moscas submetidas ao tratamento com doxorrubicina (DXR) (0,4mM) acusaram uma frequência de 2,65 tumores/mosca, demostrando a indução tumoral do controle positivo.…”

“…Para atuar como agente indutor de tumor e controle positivo foi utilizado o cloridrato de Doxorrubicina (DXR), denominado comercialmente como Adriblastina® (CAS 25316-40-9;Lote 19H0693), apresentando atividade recombinogênica e carcinogênica comprovada em D. melanogaster (BRAGA et al, 2018;LIMA et al, 2018;OR-SOLIN;LAHLOU;ORSOLIN, 2018;VASCONCELOS et al, 2017). O mesmo é produzido pelo laboratório Pfizer sob a forma de ampola com conteúdo de 50mg.…”

Exploring the therapeutic potential of Neem (Azadirachta Indica) for the treatment of prostate cancer: a literature review

“…These results support a tumor suppressive action of Neem in AR associated PCa. It may be noted that ethanolic extract of Neem leaves (EENL) was found to decrease the relative expression of AR after 48 hours of treatment at 1.0 µg/mL in MCF-7 and MDA-MB-231 breast cancer cell lines ( 119 ). Thus, the effect of Neem on the AR pathway was not confined to PCa alone.…”

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

“…Natural product-derived compounds are being extensively explored as potential cancer treatments, specially to overcome resistance and side effects, and to prolong patient's overall survival [38,39]. Considering ER-positive BC, is desirable to develop new therapeutic agents that modulate ER expression achieving greater effectiveness, with less side effects impairing thrombosis and pulmonary embolism detected in 10 years-treated patients [40,41].…”

“…The Epithelial Tumor test (ETT) has been used to detect epithelial tumor clones (Warts) in Drosophila melanogaster. This test evaluates the carcinogenic, anticarcinogenic, chemopreventive, and modulatory potential of different substances [38,43,44]. The test stands outs for its sensibility and reliability as a toxicological test and detects the loss of heterozygosity of the wts tumor suppressor gene, which leads to uncontrolled cell proliferation and the consequent formation of epithelial tumors [45].…”