RESUMO
Breast cancer (BC) is a major contributor of cancer-associated mortality in women. It is essential to find new therapeutic targets and drugs. Polyrhachis vicina Rogers is one of the Traditional Chinese Medicine (TCM). Our previous studies have shown an active fraction of Polyrhachis vicina Rogers (AFPR) has significant anti-inflammatory activity, suggesting its anti-cancer effect. Here, we aimed to explore the inhibitory effects of AFPR on BC and reveal its mechanism. The effects of AFPR on BC were examined by cell proliferation assay, wound healing assay, invasion assay and xenograft assay. Microarray sequencing, qRT-PCR, Western blot, chromatin immunoprecipitation assay and luciferase reporter assay were performed to investigate the regulation of AFPR on related genes and underlying mechanisms. As a result, AFPR suppressed BC cell growth, migration and invasion and inhibited tumor growth. LncRNA NKILA was most prominently upregulated in AFPR-treated MCF7 cells. AFPR inactivated NF-κB signaling pathway via regulating NKILA. Furthermore, AFPR regulated the expression of NKILA by inhibiting its transcript suppressor EGR1. This study firstly indicated that AFPR was a potential inhibitor of BC development via regulating EGR1/NKILA/NF-κB axis.
Assuntos
Formigas/química , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Movimento Celular/efeitos dos fármacos , Fracionamento Químico , Proteína 1 de Resposta de Crescimento Precoce/genética , Feminino , Humanos , Células MCF-7 , Masculino , Medicina Tradicional Chinesa , Camundongos Nus , NF-kappa B/genética , Invasividade Neoplásica , Neoplasias Experimentais , RNA Longo não Codificante/genética , Regulação para CimaRESUMO
Seven new α,ß-diphenyl-γ-butyrolactones (1-7), three new lignans (8-10), five new neolignans (11-15), two new 1,3-biphenylpropanoids (16 and 17), and a new flavonol galactoside-lignan ester (18), together with 43 known compounds (19-61), were isolated from the twigs of Cinnamomum cassia. Their structures were elucidated by spectroscopic data analysis as well as chemical methods. The α,ß-diphenyl-γ-butyrolactones are a class of unique natural compounds that have only been isolated from C. cassia. Compounds 11 and 12 are rare examples of neolignans possessing a 1,2-dioxetane moiety. Compound 13 is a new oxyneolignan possessing a unique C-9-O-C-9' linkage between the benzopyran and cinnamyl alcohol moieties. Compound 15 is the first example of a natural neolignan possessing a 2-styryl-3-phenyltetrahydrofuran skeleton. The isolated compounds were evaluated for their neuroprotective activities against tunicamycin-induced cytotoxicity in SH-SY5Y cells. Compounds 3, 5, 10, 11, 12, 20, 36, and 56 showed statistically significant neuroprotective activity with EC50 values ranging between 21 and 75 µM.