RESUMO
Fourteen new monoterpene-flavonoid conjugates including four monoterpene-conjugated chalcones (glabratins A-D, 1-4), seven monoterpene-conjugated dihydrochalcones (glabratins E-K, 5-11), and three monoterpene-conjugated flavanones (glabratins L-N, 12-14), together with four known analogues (15-18) were isolated from the aerial parts of Sarcandra glabra. The structures and the absolute configurations of these compounds were elucidated by the spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1, 4-6, 9-14, and 18 showed obvious cell autophagy-inducing activities at 25 µM in HEK293 cells. Furthermore, the bioassay results also showed that 18 induced cell autophagy in a dose dependent manner. Our findings revealed a rare class of monoterpene-flavonoid conjugates in nature and firstly reported their autophagy-inducing activities.
Assuntos
Autofagia/efeitos dos fármacos , Flavonoides/farmacologia , Magnoliopsida/química , Monoterpenos/farmacologia , Extratos Vegetais/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Células HEK293 , Humanos , Estrutura Molecular , Monoterpenos/química , Monoterpenos/isolamento & purificação , Método de Monte Carlo , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
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.