Total coumarins of Pileostegia tomentella induces cell death in SCLC by reprogramming metabolic patterns, possibly through attenuating ß-catenin/AMPK/SIRT1.

BACKGROUND: Small-cell lung cancer (SCLC) is a high malignant and high energy-consuming type of lung cancer. Total coumarins of Pileostegia tomentella (TCPT) from a traditional folk medicine of Yao minority, is a potential anti-cancer mixture against SCLC, but the pharmacological and molecular mechanism of TCPT remains largely unknown. METHODS: Screening of viability inhibition of TCPT among 7 cell lines were conducted by using CCK-8 assays. Anti-proliferative activities of TCPT in SCLC were observed by using colony formation and flow cytometry assays. Morphological changes were observed by transmission electron microscope and Mito-Tracker staining. High Throughput RNA-seq analysis and bio-informatics analysis were applied to find potential targeted biological and signaling pathways affected by TCPT. The mRNA expression of DEGs and protein expression of signalling proteins and metabolic enzymes were verified by qPCR and Western blot assays. Activity of rate-limiting enzymes and metabolite level were detected by corresponding enzyme activity and metabolites kits. Xenograft nude mice model of SCLC was established to observe the in vivo inhibition, metabolism reprogramming and mechanism of TCPT. RESULTS: TCPT treatment shows the best inhibition in SCLC cell line H1688 rather than other 5 lung cancer cell lines. Ultrastructural investigation indicates TCPT induces mitochondria damage such as cytoplasm shrinkage, ridges concentration and early sight of autolysosome, as well as decrease of membrane potential. Results of RNA-seq combined bio-informatics analysis find out changes of metabolism progression affected the most by TCPT in SCLC cells, and these changes might be regulated by ß-catenin/AMPK/SIRT1 axis. TCPT might mainly decline the activity and expression of rate-limiting enzymes, OGDH, PDHE1, and LDHA/B to reprogram aerobic oxidation pattern, resulting in reduction of ATP production in SCLC cells. Xenograft nude mice model demonstrates TCPT could induce cell death and inhibit growth in vivo. Assimilate to the results of in vitro model, TCPT reprograms metabolism by decreasing the activity and expression of rate-limiting enzymes (OGDH, PDHE1, and LDHA/B), and attenuates the expression of ß-catenin, p-ß-catenin, AMPK and SIRT1 accordance with in vitro data. CONCLUSION: Our results demonstrated TCPT induces cell death of SCLC by reprograming metabolic patterns, possibly through attenuating master metabolic pathway axis ß-catenin/AMPK/SIRT1.

Active fraction of Polyrhachis vicina Rogers (AFPR) suppressed breast cancer growth and progression via regulating EGR1/lncRNA-NKILA/NF-κB axis.

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.

Antidepressant-like effect of active fraction of Polyrhachisvicina Roger in a rat depression model.

OBJECTIVE: To investigate the antidepressant-like effect of active fraction of Polyrhachis vicina Roger (AFPR) in a rat depression model, and to elucidate the underlying mechanism. METHODS: AFPR was extracted with ethanol followed by petroleum ether. Its antidepressant-like effect was investigated in mice by tail suspension test (TST), forced swimming test (FST) and open field test (OPT). A repeated dose of reserpine (0.5 mg/kg, daily for 14 d) was used to establish a rat depression model. Fluoxetine was used as positive control agent. The effect of AFPR on reserpine-induced ptosis, hypothermia and akinesia, the levels of monoamines and their metabolites, and the activity of monoamine oxidase (MAO) in hippocampus and prefrontal cortex were determined. RESULTS: Administration of AFPR by gavage at 160 and 320 mg/kg significantly reduced the duration of immobility in the FST and TST, and did not affect locomotor activity in the OPT. In the reserpine-induced depression model, AFPR attenuated anhedonia, demonstrated by reversing hypothermia, akinesia and sucrose consumption. AFPR significantly increased the concentration of monoamines, including dopamine, serotonin, noradrenaline and acetylcholine. CONCLUSION: AFPR normalized the metabolism rates of noradrenaline, serotonin and dopamine, and the activity of MAO, which were altered by chronic reserpine exposure. The findings suggest that modulation of the monoaminergic neurotransmitter system likely underlies the antidepressant-like effect of AFPR.

[Chemical Constituents from Macaranga denticulata Root].

OBJECTIVE: To study the chemical constituents from Macaranga denticulata Root. METHODS: The chemical constituents were isolated and purified by silica-gel column chromatography and recrystallization, and their structures were identified by physicochemical properties and spectral data. RESULTS: Nine compounds were isolated and identified as: gheddic acid (1), aleuritolic acid-3-acetate (2), ß-sitosterol (3), stigmast-4-en-6ß-ol-3 -one (4), 2α-hydroxyaleuritolic acid 3-p-hydroxybenzoate (5), scopoletin (6), daucosterol (7), 2, 6-dimethoxy-1,4-benzoquinone (8) and maslinic acid(9). CONCLUSION: Compounds 1-9 are obtained from this plant for the first time.

[Chemical constituents of Desmodium caudatum].

OBJECTIVE: To study the chemical constituents of Desmodium caudatum. METHODS: Silica column chromatography, Sephadex LH-20 column chromatography and recrystallization were used to separate and purify the chemical composition of Desmodium caudatum. Their chemical structures were identified by infrared spectrum (IR), mass spectrum (MS), nuclear magnetic resonance (NMR) and other physicochemical methods. RESULTS: Twelve compounds were isolated and identified as lacceroic acid(1), gheddic acid(2), stigmasterol(3), betulin(4), citrusinol(5), yukovanol(6), kaempferol(7), protocatechuic acid(8), sophocarpine(9), matrine(10), N, Ndimethyltryptamine(11) and 5-hydroxy-N,N-dimethyltryptamine(12). CONCLUSION: Compounds 1, 2, 4 and 8-12 are isolated from this plant for the first time.