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1.
Front Pharmacol ; 14: 1243727, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026959

RESUMO

Objective: Non-small cell lung cancer (NSCLC) is recognized for its aggressive nature and propensity for high rates of metastasis. The NLRP3 inflammasome pathway plays a vital role in the progression of NSCLC. This study aimed to investigate the effects of S. exigua extract and its active compounds on NLRP3 regulation in NSCLC using an in vitro model. Methods: S. exigua was extracted using hexane, ethyl acetate and ethanol to obtain S. exigua hexane fraction (SE-Hex), S. exigua ethyl acetate fraction (SE-EA), and S. exigua ethanol fraction (SE-EtOH) respectively. The active compounds were identified using column chromatography and NMR analysis. A549 cells were primed with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) for activated NLRP3 inflammasome. The anti-inflammatory properties were determined using ELISA assay. The anti-proliferation and anti-metastasis properties against LPS-ATP-induced A549 cells were determined by colony formation, cell cycle, wound healing, and trans-well migration and invasion assays. The inflammatory gene expressions and molecular mechanism were determined using RT-qPCR and Western blot analysis, respectively. Results: SE-EA exhibited the greatest anti-inflammation properties compared with other two fractions as evidenced by the significant inhibition of IL-1ß, IL-18, and IL-6, cytokine productions from LPS-ATP-induced A549 cells in a dose-dependent manner (p < 0.05). The analysis of active compounds revealed exiguaflavanone A (EGF-A) and exiguaflavanone B (EGF-B) as the major compounds present in SE-EA. Then, SE-EA and its major compound were investigated for the anti-proliferation and anti-metastasis properties. It was found that SE-EA, EGF-A, and EGF-B could inhibit the proliferation of LPS-ATP-induced A549 cells through cell cycle arrest induction at the G0/G1 phase and reducing the expression of cell cycle regulator proteins. Furthermore, SE-EA and its major compounds dose-dependently suppressed migration and invasion of LPS-ATP-induced A549 cells. At the molecular level, SE-EA, EGF-A, and EGF-B significantly downregulated the mRNA expression of IL-1ß, IL-18, IL-6, and NLRP3 in LPS-ATP-induced A549 cells. Regarding the mechanistic study, SE-EA, EGF-A, and EGF-B inhibited NLRP3 inflammasome activation through suppressing NLRP3, ASC, pro-caspase-1(p50 form), and cleaved-caspase-1(p20 form) expressions. Conclusion: Targeting NLRP3 inflammasome pathway holds promise as a therapeutic approach to counteract pro-tumorigenic inflammation and develop novel treatments for NSCLC.

2.
BMC Complement Med Ther ; 23(1): 191, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296375

RESUMO

BACKGROUND AND AIMS: The purpose of this study was to investigate the biological properties of Kae-Lae (Maclura cochinchinensis (Lour.) Corner), a traditional medicinal plant used in Ayurvedic recipes in Thailand. To achieve this objective, heartwood samples were collected from 12 sources across Thailand. Fractional extracts (n-hexane, ethyl acetate, and ethanol) and the dominant compounds (morin, resveratrol, and quercetin) were examined for their abilities on cytotoxicity, antioxidant, anti-inflammation, and antileukaemic activity (Wilms' tumour 1 protein was used as a well-known biomarker for leukaemic cell proliferation). METHODS: The study used MTT to assess cytotoxicity in leukaemic cells (K562, EoL-1, and KG-1a). Antioxidant activities were evaluated using ABTS, DPPH, and FRAP assays. The anti-inflammatory activity was investigated by detecting IL-2, TNF-α, and NO using appropriate detection kits. Wilms' tumour 1 protein expression was measured by Western blotting to determine the anti-leukaemic activity. The inhibition of cell migration was also analyzed to confirm anticancer progression. RESULTS: Among the tested extract fraction, ethyl acetate No. 001 displayed strong cytotoxicity specifically in EoL-1 cells, while n-hexane No. 008 demonstrated this effect in three cell lines. Resveratrol, on the other hand, displayed cytotoxicity in all the tested cells. Additionally, the three major compounds, morin, resveratrol, and quercetin, exhibited significant antioxidant and anti-inflammatory properties. In particular, resveratrol demonstrated a noteworthy decreased Wilms' tumour 1 protein expression and a reduction in cell proliferation across all cells. Moreover, ethyl acetate No. 001, morin, and resveratrol effectively inhibited MCF-7 cell migration. None of these compounds showed any impact on red blood cell haemolysis. CONCLUSION: Based on these findings, it can be concluded that Kae-Lae has promising chemotherapeutic potential against leukaemic cells, with fractional extracts (ethyl acetate and n-hexane) and resveratrol exhibiting the most potent cytotoxic, antioxidant, anti-inflammatory, and anti-cell migration activities.


Assuntos
Antioxidantes , Maclura , Humanos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Flavonoides/farmacologia , Maclura/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Quercetina , Resveratrol , Tailândia , Proteínas WT1/metabolismo
3.
Nat Prod Res ; 35(6): 988-992, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31135208

RESUMO

The magnolia plant has been used in traditional medicine since ancient times. This study was designed to investigate the effects of active compounds from Thai Champi Sirindhorn (Magnolia sirindhorniae) on leukemic biomarker Wilms' tumor 1 (WT1) protein expressions in K562 and Molt-4 cells. Costunolide (1) and parthenolide (2) were the major components used in this study, they were purified from ethyl acetate fractions. Costunolide (1) and parthenolide (2) had strong cytotoxic effects in K562 and Molt-4 cells measured with MTT assays. Their activities were compared to standard commercial costunolide (3) and parthenolide (4). Costunolide (1) and parthenolide (2) decreased WT1 protein levels and total cell numbers in K562 and Molt-4 cells. Both purified costunolide (1) and standard commercial costunolide (3) decreased WT1 protein levels in a time- and dose-dependent manner. Therefore, the active compounds from M. sirindhorniae were identified as promising sources for bioactive compounds for further applications in traditional medicine.


Assuntos
Magnolia/química , Sesquiterpenos/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Células K562 , Extratos Vegetais/farmacologia , Sesquiterpenos/química , Tailândia
4.
BMC Complement Altern Med ; 16: 130, 2016 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-27193767

RESUMO

BACKGROUND: Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compound from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, WT1 protein and mRNA stability, and cell proliferation in K562 cell line. METHODS: M. siamensis seeds were obtained from the region of Chiang Mai (North of Thailand). Mammea E/BB was extracted from seeds of M. siamensis. WT1 protein expression and stability were evaluated by Western blot analysis. WT1 mRNA stability was assessed by qRT-PCR. WT1-DNA binding and WT1 promoter activity were assayed by ChIP assay and luciferase-reporter assay, respectively. Cell cycle arrest was studied by flow cytometry. RESULTS: Treatment with mammea E/BB led to down-regulation of WT1 expression. The suppression of WT1 expression did not involve protein and mRNA degradation. Rather, WT1 protein was down-regulated through disruption of transcriptional auto-regulation of the WT1 gene. Mammea E/BB inhibited WT1-DNA binding at the WT1 promoter and decreased luciferase activity. It also disrupted c-Fos/AP-1 binding to the WT1 promoter via ERK1/2 signaling pathway and induced S phase cell cycle arrest in K562 cells. CONCLUSION: Mammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation.


Assuntos
Cumarínicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Mammea/química , Extratos Vegetais/farmacologia , Proteínas WT1/biossíntese , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Humanos , Células K562 , Estrutura Molecular , Estabilidade de RNA/efeitos dos fármacos , RNA Neoplásico , Proteínas WT1/genética
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