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Bletilla striata (Thunb.) Rchb.f., a medicinal plant in the Orchidaceae family, is mainly found in East Asia and has extensive pharmacological activities. Plant's volatile components are important active ingredients with a wide range of physiological activities, and B. striata has a special odor and unique volatile components. Yet it has received little attention, hindering a full understanding of its phytochemical components. Employing the ultrasonic-assisted extraction method, the volatile components of B. striata's fibrous root, bud, aerial part and tuber were extracted, resulting in yields of 0.06%, 0.64%, 3.38% and 4.47%, respectively. A total of 78 compounds were identified from their chemical profiles using gas chromatography-mass spectrometry (GC-MS), including 45 components with the main compounds of linoleic acid (content accounting for 31.23%), n-hexadecanoic acid (13.53%), and octadecanoic acid (9.5%) from the tuber, 34 components with the main compounds of eicosane, 2-methyl- (28.42%), linoelaidic acid (10.43%), linoleic acid (4.53%), and n-hexadecanoic acid (6.91%) from the fibrous root, 38 components with the main compounds of pentadeca-6,9-dien-1-ol (9.29%), n-hexadecanoic acid (11%), eicosane,2-methyl- (23.43%), and linoleic acid (23.53%) from the bud, and 27 components with the main compounds of linoelaidic acid (5.97%), n-hexadecanoic acid (15.99%), and linolenic acid ethyl ester (18.9%) from the aerial part. Additionally, the growth inhibition activity against colon cancer HCT116 cells was evaluated using sulforhodamine B (SRB) assay and the thiazolyl blue tetrazolium bromide (MTT) assay, and the accumulation of reactive oxygen species (ROS) was determined using dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining and fluorescence intensity analysis. The volatile extracts exhibited significant growth inhibitory efficacy against HCT116 cells, with half-maximal inhibitory concentration (IC50) values of 3.65, 2.32, 2.42 and 3.89 mg/mL in the SRB assay, and 3.55, 2.58, 3.12 and 4.80 mg/mL in the MTT assay for the root, bud, aerial part, and tuber, respectively. Notably, treatment with the aerial part extract caused morphological changes in the cells and significantly raised the intracellular ROS level. In summary, the chemical profiles of the volatile components of B. striata were revealed for the first time, demonstrating a certain tissue specificity. Additionally, it demonstrated for the first time that these volatile extracts possess potent anti-colon cancer activity, highlighting the importance of these volatile components in B. striata's medicinal properties.
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Adenosine, as a naturally occurring nucleoside, plays an important role in human health maintenance. In recent years, many studies have shown that adenosine has the effect of cancer inhibition, and some of its analogs have been successfully marketed as anticancer drugs. This report mainly describes the anti-colon cancer activities and mechanism of a novel halogenated adenosine analog named 5'-bromodeoxyadenosine (5'-BrDA). As a result, 5'-BrDA concentration-dependently inhibited colon cancer cells proliferation, induced autophagy without disruption of lysosomal stability, and promoted autophagy-independently cellular mitochondrial apoptosis by increasing the accumulation of reactive oxygen species. Furthermore, 5'-BrDA inhibited the tumor growth of colon cancer in CT26 inbred mice without affecting the body weight in vivo. Collectively, the above-mentioned mechanisms contributed to the anticancer activity of 5'-BrDA. It is rare to discover novel anticancer adenosine analogs during the past couple of decades. We believe that our work will enrich the understanding of adenosine analogs, also, pave the way for adenosine analogs product based anticancer drug development.
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Adenosina/farmacologia , Neoplasias do Colo/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Células HCT116 , Células HT29 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Dietary phytochemicals play an important role in the prevention and treatment of colon cancer. It is reported that group B of soyasaponin, derived from dietary pulses, has anti-colonic effects on some colon cancer cell lines. However, it is uncertain which specific soybean saponins play a role. In our study, as one of the group B soyasaponin, the anti-colon cancer activity of soyasaponins I (SsI) was screened, and we found that it had the inhibitory effect of proliferation on colon cancer cell lines HCT116 (IC50 = 161.4 µM) and LoVo (IC50 = 180.5 µM), but no effect on HT29 between 0-200 µM. Then, nine potential targets of SsI on colon cancer were obtained by network pharmacology analysis. A total of 45 differential metabolites were identified by metabolomics analysis, and the KEGG pathway was mainly enriched in the pathways related to the absorption and metabolism of amino acids. Finally, molecular docking analysis predicted that SsI might dock with the protein of DNMT1, ERK1. The results indicated that the effect of SsI on HCT116 might be exerted by influencing amino acid metabolism and the estrogen signaling pathway. This study may provide the possibility for the application of SsI against colon cancer.
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Neoplasias do Colo , Ácido Oleanólico , Saponinas , Neoplasias do Colo/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Compostos Fitoquímicos/farmacologia , Saponinas/farmacologiaRESUMO
Numerous health benefits of diets containing red seaweeds or agar-derived sugar mixtures produced by enzymatic or acid hydrolysis of agar have been reported. However, among various agar-derived sugars, the key components that confer health-beneficial effects, such as prebiotic and anti-colon cancer activities, remain unclear. Here, we prepared various agar-derived sugars by multiple enzymatic reactions using an endo-type and an exo-type of ß-agarase and a neoagarobiose hydrolase and tested their in vitro prebiotic and anti-colon cancer activities. Among various agar-derived sugars, agarotriose exhibited prebiotic activity that was verified based on the fermentability of agarotriose by probiotic bifidobacteria. Furthermore, we demonstrated the anti-colon cancer activity of 3,6-anhydro-l-galactose, which significantly inhibited the proliferation of human colon cancer cells and induced their apoptosis. Our results provide crucial information regarding the key compounds derived from red seaweeds that confer beneficial health effects, including prebiotic and anti-colon cancer activities, to the host.
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Ágar/metabolismo , Antineoplásicos/farmacologia , Bifidobacterium/metabolismo , Neoplasias do Colo/tratamento farmacológico , Galactose/análogos & derivados , Prebióticos , Rodófitas/metabolismo , Alga Marinha/metabolismo , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Fermentação , Galactose/isolamento & purificação , Galactose/farmacologia , Células HCT116 , Humanos , HidróliseRESUMO
Bioactive compounds released during milk fermentation by proteolytic cleavage of milk proteins have a role beyond their nutritional importance. This study assessed the proteolytic activity of Lactobacillus helveticus strains ASCC953, ASCC474, ASCC1188, and ASCC1315 and their ability to release bioactive compounds capable of exerting antioxidative and in vitro anticarcinogenic properties during incubation at 37°C in reconstituted skim milk. The performance of these strains was not affected by the pH decline during fermentation. Soluble extracts of fermented milk by L. helveticus 474 showed the highest free radical (1,1-diphenyl-2-picrylhydrazyl) scavenging activity at 12 h of fermentation, followed by a significant reduction of this activity at 24 h compared with the other strains and control (untreated milk). Skim milk fermented by L. helveticus strains contained compounds with anti-colon cancer activity at varied levels during fermentation. The activity (19.03-50.98% growth inhibition) was greatest in the extract obtained after 12 h of fermentation, which markedly declined (5.4-9.94%) at the end of fermentation. Lactobacillus helveticus 1315 released compounds into the skim milk supernatant with a greater growth inhibition (50.98%) on colon cancer HT-29 cell line than the other strains. More importantly, these compounds had no significant inhibition effect on normal, primary colon cells T4056. Whereas these results suggest that milk fermented by L. helveticus strains may release bioactive compounds with important multifunctional properties, the characteristics and activities of these compounds appear highly strain- and fermentation time-dependent.
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Antineoplásicos/química , Antioxidantes/química , Lactobacillus helveticus/metabolismo , Proteínas do Leite/química , Leite/química , Animais , Neoplasias do Colo/tratamento farmacológico , Fermentação , Células HT29 , Humanos , Lactobacillus helveticus/genética , ProteóliseRESUMO
In order to modify colonic release behavior of lactoferrin (Lf), a hydrophobic composite nanofibrous carrier (CNC) was constructed by emulsion coaxial electrospinning. Ethylcellulose/pectin based water-in-oil emulsion and Lf-contained polyvinyl alcohol solution were used as shell and core fluids, respectively. An electrospinning diagram was first constructed to screen out suitable viscosity (51-82 cP) and conductivity (960-1300 µS/cm) of the dispersed phase of pectin solution for successful electrospinning of shell emulsion. Varying mass fraction of pectin solution (5 %-20 %) of shell emulsion during emulsion coaxial electrospinning obtained CNCs with different micro-structures, labeled as 5&95 CNC, 10&90 CNC, 15&85 CNC, 20&80 CNC. These CNCs all achieved colonic delivery of Lf (>95 %), and the time for complete release of Lf in simulated colon fermentation process were 10, 7, 5 and 3 h, respectively. That is, the greater the pectin content in CNC, the faster the release rate of stabilized Lf in colon. Lf release in simulated colon fermentation fluid involved complex mechanisms, in which diffusion release of Lf was dominant. Increasing colonic release rate of Lf enhanced its regulation effect on the expression levels of cell cycle arrest and apoptosis-related protein and promote its effective inhibition on the proliferation of HCT116 cell.
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Celulose/análogos & derivados , Neoplasias do Colo , Nanofibras , Humanos , Pectinas/química , Lactoferrina/química , Emulsões/química , Neoplasias do Colo/tratamento farmacológicoRESUMO
Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.
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Antineoplásicos , Aspergillus , Compostos de Enxofre , Humanos , Aspergillus/química , Estrutura Molecular , Células HCT116 , Compostos de Enxofre/farmacologia , Compostos de Enxofre/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/isolamento & purificação , Células CACO-2 , Neoplasias do Colo/tratamento farmacológicoRESUMO
As a leading global cause of mortality, cancer continues to pose a significant challenge. The shortcomings of prevalent cancer treatments, such as surgery, radiation therapy, and chemotherapy, necessitate the exploration of alternative therapeutic strategies. Selenium nanoparticles (SeNPs) have emerged as a promising solution, with their synthesis being widely researched due to their potential applications. Among the diverse synthesis methods for SeNPs, the green chemistry approach holds a distinctive position within nanotechnology. This research delves into the anti-proliferative and anticancer properties of green-synthesized SeNPs via the cell-free supernatant (CFS) of Lactobacillus casei (LC-SeNPs), with a specific focus on MCF-7 and HT-29 cancer cell lines. SeNPs were synthesized employing the supernatant of L. casei. The characterization of these green-synthesized SeNPs was performed using TEM, FE-SEM, XRD, FT-IR, UV-vis, energy-dispersive X-ray spectroscopy, and DLS. The biological impact of LC-SNPs on MCF-7 and HT-29 cancer cells was examined via MTT, flow cytometry, scratch tests, and qRT-PCR. Both FE-SEM and TEM images substantiated the spherical shape of the synthesized nanoparticles. The biosynthesized LC-SNPs reduced the survival of MCF-7 (by 20%) and HT-29 (by 30%) cells at a concentration of 100 µg/mL. Flow cytometry revealed that LC-SNPs were capable of inducing 28% and 23% apoptosis in MCF-7 and HT-29 cells, respectively. In addition, it was found that LC-SNPs treated MCF-7 and HT-29 cells were arrested in the sub-G1 phase. Gene expression analysis indicated that the expression levels of the CASP3, CASP9, and BAX genes were elevated after treating MCF-7 and HT-29 cells with LC-SNPs. Further, SeNPs were observed to inhibit migration and invasion of MCF-7 and HT-29 cancer cells. The SeNPs, produced via L. casei, demonstrated strong anticancer effects on MCF-7 and HT-29 cells, suggesting their potential as biological agents in cancer treatment following additional in vivo experiments.
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Neoplasias da Mama , Neoplasias do Colo , Lacticaseibacillus casei , Nanopartículas , Selênio , Humanos , Feminino , Selênio/metabolismo , Neoplasias da Mama/tratamento farmacológico , Células HT29 , Células MCF-7 , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Neoplasias do Colo/tratamento farmacológico , Apoptose , Pontos de Checagem do Ciclo CelularRESUMO
Caulerpa lentillifera is rich in polysaccharides, and its polysaccharides show a significant effect in different biological activities including anti-cancer activity. As an edible algae-derived polysaccharide, exploring the role of colon cancer can better develop the application from a dietary therapy perspective. However, more in-depth studies of C. lentillifera polysaccharide on anti-colon cancer activity and mechanism are needed. In this study, we found that Caulerpa lentillifera polysaccharides (CLP) showed potential anti-colon cancer effect on human colon cancer cell HT29 in monolayer (IC50 = 1.954 mg/mL) and spheroid (IC50 = 0.402 mg/mL). Transcriptomics and metabolomics analyses revealed that CLP had an inhibitory effect on HT29 3D spheroid cells by activating aminoacyl-tRNA biosynthesis as well as arginine and proline metabolism pathways. Furthermore, the anti-colon cancer effects of CLP were confirmed through other human colon cancer cell HCT116 and LoVo in monolayer cells (IC50 = 1.890 mg/mL and 1.437 mg/mL, respectively) and 3D spheroid cells (IC50 = 0.344 mg/mL and 0.975 mg/mL, respectively), and three patient-derived organoids with IC50 values of 6.333-8.780 mg/mL. This study provided basic data for the potential application of CLP in adjuvant therapeutic food for colon cancer on multiple levels, while further investigation of detailed mechanism in vivo was still required.
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Caulerpa , Neoplasias do Colo , Algas Comestíveis , Polissacarídeos , Esferoides Celulares , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Caulerpa/química , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Técnicas de Cultura de Células em Três Dimensões/métodos , Proliferação de Células/efeitos dos fármacos , Células HT29 , Linhagem Celular Tumoral , Células HCT116 , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Oxypeucedanin (OPD) as a powerful anti-proliferative agent found in the Angelicae dahuricae has been used to suppress cancer cell growth. However, the hydrophobic chemical structure has limited its solubility and bio-accessibility. This is the first time OPD is encapsulated into a nano-liposomal structure and coated with poly-cationic chitosan polymer as the oxypeucedanin drug delivery system to evaluate its antioxidant and anti-colon cancer potential. The chitosan-coated oxypeucedanin nano-chitosomes (COPD-NCs) were synthesized utilizing the thin-layer hydration method and characterized by FESEM, DLS, FTIR, and zeta potential analysis. The anti-cancer potential of COPD-NC was analyzed by measuring the cell survival rate (MTT assay) and studying the cellular death type (AO/PI staining) following the increased treatment concentrations of COPD-NC on the HT-29 colon cancer cell line. Moreover, the COPD-NCs' apoptotic activity was verified by analyzing Cas-3 and Cas-9 gene expression profiles. Finally, the COPD-NCs' antioxidant activity was evaluated by applying ABTS, DPPH, and FRAP antioxidant assays. The 258.26-nm COPD-NCs significantly inhibited the HT-29 colon cancer cells compared with the normal fibroblast HFF cells. The up-regulated Cas-3 and Cas-9 gene expression exhibited the COPD-NCs' apoptotic activity. Also, the COPD-NCs' apoptotic activity was verified by detecting the increased apoptotic bodies following the AO/PI fluorescent staining in the increased exposure doses of COPD-NCs. Ultimately, the COPD-NCs meaningfully inhibited the ABTS-DPPH radicals and exhibited an appropriate FRAP-reductive potential. The designed nanostructure for COPD-NCs significantly improved its antioxidant potential and selective cytotoxicity on human HT-29 human cancer cells, which makes them a safe selective natural drug delivery system. Therefore, the COPD-NCs can selectively induce apoptotic death in human HT-29 cancer cells and have the potential to be studied as an anti-colon cancer compound. However, further cancer and normal cell lines are required to verify their selective cytotoxicity.
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Benzotiazóis , Quitosana , Neoplasias do Colo , Furocumarinas , Doença Pulmonar Obstrutiva Crônica , Ácidos Sulfônicos , Humanos , Quitosana/química , Antioxidantes , Células HT29RESUMO
Colorectal cancer is the third most common cancer in the world, and therapies with safety are in great need. In this study, the ß-glucan isolated from Lentinus edodes was successfully fractionated into three fractions with different weight-average molecular weight (Mw) by ultrasonic degradation and used for the treatment of colorectal cancer. In our findings, the ß-glucan was successfully degraded with the Mw decreased from 2.56 × 106 Da to 1.41 × 106 Da, exhibiting the triple helix structure without conformation disruption. The in vitro results indicate that ß-glucan fractions inhibited colon cancer cell proliferation, induced colon cancer cell apoptosis, and reduced inflammation. The in vivo results based on Azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model demonstrate that the lower-molecular weight ß-glucan fraction showed stronger anti-inflammatory and anti-colon cancer activities by reconstructing intestinal mucosal barrier, increasing short chain fatty acids (SCFAs) content, regulating metabolism of gut microbiota, and rebuilding the gut microbiota structure with the increased Bacteroides and the decreased Proteobacteria at the phylum level, as well as with the decreased Helicobacter and the increased Muribaculum at the genus level. These findings provide scientific basis for using the ß-glucan to regulate gut microbiota as an alternative strategy in the clinical treatment of colon cancer.
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Neoplasias Associadas a Colite , Colite , Neoplasias do Colo , Microbioma Gastrointestinal , Cogumelos Shiitake , beta-Glucanas , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , beta-Glucanas/farmacologia , beta-Glucanas/uso terapêuticoRESUMO
Colorectal cancer (CRC) ranks third among fatal diseases afflicting mankind globally due to the shortage of primary detection methods and appropriate choice of drugs. Moreover, current treatments such as chemo drugs and radiotherapies create adverse effects and lead to drug resistance. In this context, recent advances in nanomedicine offer novel clinical solutions for colon cancer therapy. The current study denotes the therapeutic roles of biogenic Abutilon indicum silver and gold nanoparticles (AIAgNPs and AIAuNPs) against a 1, 2-dimethyl hydrazine (DMH)-induced CRC in Wistar rats. Following treatment of nanoparticles (NPs), the CRC rats showed great localization of AIAgNPs and AIAuNPs in colon tumors shown by ICP-OES, indicating their bioavailability. The AIAgNPs and AIAuNPs significantly enhanced cellular antioxidant enzyme levels including catalase, SOD, GSH, GPx and reduced lipid peroxidation (LPO) compared to the standard drug paclitaxel. AIAgNPs and AIAuNPs revealed significant protection against metastasis compared to paclitaxel shown in the histopathological study. The important CRC signaling molecules of the Wnt pathway, the ß-catenin and Tcf-4 levels were significantly downregulated in AIAgNPs and AIAuNPs treated CRC rats compared to paclitaxel. Furthermore, the expression levels of cleaved apoptotic caspase-9, -8, and - 3 and lamins were significantly upregulated in AIAgNPs and AIAuNPs treated CRC rats compared to paclitaxel. This preclinical study provides substantial insights into the anti-colon cancer roles of biogenic NPs and gives an idea for targeting different cancers.
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Neoplasias do Colo , Nanopartículas Metálicas , Animais , Ratos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Ouro , Nanopartículas Metálicas/uso terapêutico , Paclitaxel/efeitos adversos , Ratos Wistar , Prata/uso terapêutico , 1,2-Dimetilidrazina/farmacologiaRESUMO
Colon cancer is the third most prevalent cancer and the second most deadly cancer in the world. Anti-colon cancer activity of Agaricus bisporus polysaccharides has not been studied. In this paper, Agaricus bisporus polysaccharides were sequentially extracted by room temperature water, hot water, high pressure hot water, dilute alkaline solution and concentrated alkaline solution. A homogeneous polysaccharide (WAAP-1) was obtained using DEAE Cellulose-52 column. Physicochemical properties, structural characterization and anti-colon cancer activity of WAAP-1 were investigated. The results showed that WAAP-1 was a neutral polysaccharide with molecular weight of 10.1 kDa. The monosaccharide composition was glucose, mannose and galactose with a molar ratio of 84.95:8.97:4.50. The main chain was mainly composed of (1,4)-α-D-Glcp and (1,6)-ß-D-Manp. In vitro anti-colon cancer results showed that WAAP-1 could significantly inhibit proliferation of colon cancer cell HT-29. It promoted apoptosis and inhibited epithelial mesenchymal transition of HT-29 by up-regulating the expression of Caspase-3, Bax and E-cadherin proteins and down-regulating the expression of Bcl-2 and Vimentin proteins. The results provided new potential possibilities for the development of novel functional foods or antitumor drugs.
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Colon cancer, a prevalent malignant tumor affecting the digestive system, presents a substantial risk to human health due to its high occurrence and mortality rates. Phellinus baumii polyphenol (PBP), a natural product derived from traditional Chinese medicine, has gained widespread popularity due to its low toxicity and minimal side effects, compared to radiation and chemotherapy. This study used an integrated approach of network pharmacology and experimental verification to elucidate the anti-colon cancer effects of PBP and its potential mechanisms. In network pharmacology, the identification of relevant targets involved a comprehensive search across multiple databases using keywords such as "active components of PBP" and "colon cancer". Venn diagram analysis was subsequently performed to ascertain the shared targets. To identify the key active components and core targets, we constructed a network of "Disease-Drug-Pathways-Targets" and a protein-protein interaction (PPI) network among the targets using Cytoscape 3.9.1. Furthermore, molecular docking was carried out to predict the binding affinity and conformation between the main active compounds (davallialactone and citrinin) of PBP and the core targets (TP53, STAT3, CASP3, CTNNB1, PARP1, MYC). To validate our findings, in vitro experiments were conducted. We verified that PBP exerted an anti-colon cancer effect on human colon cancer HCT116 cells by significantly inhibiting cell proliferation, promoting apoptosis and arresting the cell cycle in S phase by using Cell Counting Kit-8 (CCK-8) and flow cytometry. Finally, we determined the key regulatory proteins related to apoptosis and the cell cycle by western blot analysis, and proposed the potential mechanism by which PBP exerts an anti-colon cancer effect by inducing the caspase-dependent mitochondrial-mediated intrinsic apoptotic pathway and arresting the cell cycle in S phase in HCT116 cells. These results suggest that PBP possesses substantial potential for the treatment of colon cancer and may serve as a viable alternative therapeutic strategy in colon cancer treatment.
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Basidiomycota , Neoplasias do Colo , Medicamentos de Ervas Chinesas , Humanos , Farmacologia em Rede , Simulação de Acoplamento Molecular , Neoplasias do Colo/tratamento farmacológicoRESUMO
We have obtained an exopolysaccharide (YL-11 EPS) produced by Lactobacillus fermentum YL-11 isolated from fermented milk and confirmed that it can effectively inhibit colon cancer HT-29 cells proliferation in vitro. The aim of this study is to study anti-colon cancer effect in vivo and its possible mechanisms. Animal assays indicated YL-11 EPS treatment significantly suppressed the growth of HT-29 tumor xenograft without exhibiting obvious negative effects on normal cells. Cell experiments demonstrated YL-11 EPS treatment up regulated the ratio of Bax/Bcl-2 and induced the decrease in mitochondrial membrane potential and improved the expression of cleaved caspases-3 and cleaved PARP proteins, and finally induced HT-29 cells apoptosis, suggesting the involvement of mitochondrial pathway. Moreover, YL-11 EPS can block the PI3K/AKT signaling pathway and arrest the cell cycle in G1-phase to exert its anti-colon cancer activity. Overall, YL-11 EPS can be explored as a potential nutraceutical to prevent colorectal cancer.
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Neoplasias do Colo , Limosilactobacillus fermentum , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/metabolismo , Células HT29 , Humanos , Limosilactobacillus fermentum/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Gracilaria rubra is rich in bioactive compounds with various potential health benefits. This study aimed to elucidate the profile of both extractable bioactive components (EBCs) and non-extractable bioactive components (NEBCs) of G. rubra and determine their anti-colon cancer and anti-inflammatory activities. Both EBCs and NEBCs displayed strong suppressive effects on the viability of HCT116 cells, which causes cell cycle arrest, induces cellular apoptosis, and regulates the expression of cyclin-dependent kinases (CDKs) and tumor suppressor proteins. Additionally, EBCs and NEBCs from G. rubra displayed anti-inflammatory functions via inhibiting the production of nitric oxide (NO), reactive oxygen species (ROS), and proinflammatory cytokines in activated macrophages and regulating the expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), NADPH-quinone oxidoreductase-1 (NQO-1), and heme oxygenase 1 (HO-1). These findings provide a rationale for animal and human studies designed to evaluate the chemopreventive and anti-inflammatory potential of these bioactive compounds from G. rubra.
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Polyphenols from edible seaweeds display various health benefits which have not been adequately studied. This study aimed to characterize the composition of extractable polyphenol-rich components (EPCs) and non-extractable polyphenol-rich components (NEPCs) from three edible seaweeds (i.e., Laminaria japonica, Ulva lactuca, and Porphyra tenera) and evaluate their anti-inflammatory capacities in activated macrophages and anticancer properties in colon cancer cells. Both EPCs and NEPCs from three edible seaweeds against lipopolysaccharides (LPS) stimulated nitric oxide in activated macrophages. Immunoblotting and qRT-PCR indicated that EPCs and NEPCs regulated the expression levels of proinflammatory enzymes, proinflammatory cytokines, and antioxidant enzymes in macrophages. Furthermore, EPCs and NEPCs lowered the viability of colon cancer cells, while normal colon cells were not affected. Additionally, EPCs and NEPCs induced cellular apoptosis and led to G0/G1 cell cycle arrest in HCT116 cells. Overall, these results provide a rationale for future animal and human studies designed to examine the anti-inflammatory and chemopreventive capacities of polyphenols-rich components from L. japonica, U. lactuca, and P. tenera.
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Short-chain fatty acids (SCFAs), particularly butyrate, have received considerable attention with regard to their anti-cancer efficacy in delaying or preventing colorectal cancer. Several studies have reported that certain probiotic strains could produce SCFAs; however, different strains yielded different amounts of SCFAs. This study explored the ability to produce SCFAs of the following probiotic strains: Lacticaseibacillus paracasei SD1, Lacticaseibacillus rhamnosus SD4, Lacticaseibacillus rhamnosus SD11, and Lacticaseibacillus rhamnosus GG. L. paracasei SD1 and L. rhamnosus SD11 exhibited high butyrate production, particularly when the strains were combined. The functions of the SCFAs were further characterized; the SCFAs exerted a positive anti-cancer effect in the colon via various actions, including inhibiting the growth of the pathogens related to colon cancer, such as Fusobacterium nucleatum and Porphyromonas gingivalis; suppressing the growth of cancer cells; and stimulating the production of the anti-inflammatory cytokine IL-10 and antimicrobial peptides, especially human ß-defensin-2. In addition, the SCFAs suppressed pathogen-stimulated pro-inflammatory cytokines, especially IL-8. The results of this study indicated that selected probiotic strains, particularly L. paracasei SD1 in combination with L. rhamnosus SD11, may serve as good natural sources of bio-butyrate, which may be used as biotherapy for preventing or delaying the progression of colon cancer.
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Neoplasias do Colo , Lacticaseibacillus rhamnosus , Probióticos , Humanos , Lactobacillus , Probióticos/farmacologia , Probióticos/uso terapêutico , Ácidos Graxos Voláteis , ButiratosRESUMO
This study aims to observe the effects of coix seed oil (CSO) on HT-29 cells and investigate its possible regulation mechanism of the PI3K/Akt signaling pathway. Fatty acid analysis showed that coix seed oil mainly contains oleic acid (50.54%), linoleic acid (33.76%), palmitic acid (11.74%), and stearic acid (2.45%). Fourier transform infrared results found that the fatty acid functional groups present in the oil matched well with the vegetable oil band. The results from CCK-8 assays showed that CSO dose-dependently and time-dependently inhibited the viability of HT-29 cells in vitro. CSO inhibited cell viability, with IC50 values of 5.30 mg/mL for HT-29 obtained after 24 h treatment. Morphological changes were observed by apoptotic body/cell nucleus DNA (Hoechst 33258) staining using inverted and fluorescence microscopy. Moreover, flow cytometry analysis was used to evaluate the cell cycle and cell apoptosis. It showed that CSO induced cell apoptosis and cycle arrest in the G2 phase. Quantitative real-time PCR and Western blotting revealed that CSO induced cell apoptosis by downregulating the PI3K/AKT signaling pathway. Additionally, CSO can cause apoptosis in cancer cells by activating caspase-3, up-regulating Bax, and down-regulating Bcl-2. In conclusion, the results revealed that CSO induced G2 arrest and apoptosis of HT-29 cells by regulating the PI3K/AKT signaling pathway.
RESUMO
In the present study, biocompatible manganese nanoparticles have been linked with zinc and iron molecules to prepare different derivatives of Mn0.5Zn0.5ErxYxFe2-2xO4 NPs (x = 0.02, 0.04, 0.06, 0.08, 0.10), using an ultrasonication approach. The structure, surface morphology, and chemical compositions of Mn0.5Zn0.5ErxYxFe2-2xO4 NPs were elucidated by X-ray diffractometer (XRD), High-resolution transmission electron microscopy (HR-TEM), scanning electron microscope (SEM), and Energy Dispersive X-Ray Analysis (EDX) techniques. The bioactivity of Mn0.5Zn0.5ErxYxFe2-2xO4 NPs on normal (HEK-293) and (HCT-116) colon cancer cell line was evaluated. The Mn0.5Zn0.5ErxYxFe2-2xO4 NPs treatment post 48 h resulted in a significant reduction in cells (via MTT assay, having an IC50 value between 0.88 µg/mL and 2.40 µg/mL). The specificity of Mn0.5Zn0.5ErxYxFe2-2xO4 NPs were studied by treating them on normal cells line (HEK-293). The results showed that Mn0.5Zn0.5ErxYxFe2-2xO4 NPs did not incur any effect on HEK-293, which suggests that Mn0.5Zn0.5ErxYxFe2-2xO4 NPs selectively targeted the colon cancerous cells. Using Candida albicans, antifungal activity was also studied by evaluating minimum inhibitory/fungicidal concentration (MIC/MFC) and the effect of nanomaterial on the germ tube formation, which exhibited that NPs significantly inhibited the growth and germ tube formation. The obtained results hold the potential to design nanoparticles that lead to efficient bioactivity.