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BACKGROUND: The present study aimed to elucidate the potential anticancer activity and mechanism of P. harmala's alkaloid extract, harmine (HAR), and harmaline (HAL) in HCT-116 colorectal cancer cells. METHODS AND RESULTS: P. harmala's alkaloid was extracted from harmala seeds. HCT-116 cells were treated with P. harmala's alkaloid extract, HAR and HAL. Cytotoxicity was determined by MTT assay, apoptotic activity detected via flow cytometry and acridine orange (AO)/ethidium bromide (EB) dual staining, and cell cycle distribution analyzed with flow cytometry. The mRNA expression of Bcl-2-associated X protein (Bax) and glycogen synthase kinase-3 beta (GSK3ß) was measured by real-time PCR. Furthermore, the expression of Bax, Bcl-2, GSK3ß and p53 proteins, were determined by western blotting. The findings indicated that, P. harmala's alkaloids extract, HAR and HAL were significantly cytotoxic toward HCT116 cells after 24 and 48 h of treatment. We showed that P. harmala's alkaloid extract induce apoptosis and cell cycle arrest at G2 phase in the HCT116 cell line. Downregulation of GSK3ß and Bcl-2 and upregulation of Bax and p53 were observed. CONCLUSION: The findings of this study indicate that the P. harmala's alkaloid extract has anticancer activity and may be further investigated to develop future anticancer chemotherapeutic agents.
Assuntos
Apoptose , Neoplasias do Colo , Glicogênio Sintase Quinase 3 beta , Harmina , Peganum , Sementes , Humanos , Peganum/química , Células HCT116 , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Sementes/química , Harmina/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Alcaloides/farmacologia , Harmalina/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proliferação de Células/efeitos dos fármacosRESUMO
Avermectins are a group of macrocyclic lactones that are commonly used as pesticides to treat pests and parasitic worms. Some members of the avermectin family, such as ivermectin, have been found to exhibit anti-proliferative activity toward cancer cells. This study aimed to investigate the potential anti-cancer activities of avermectin B1a using the HCT-116 colon cancer cell line. The MTT assay was used to calculate the IC50 by incubating cells with increasing doses of avermectin B1a for 24, 48, and 72 h. Flow cytometry was used to evaluate apoptosis following the 24 h incubation of cells. The migration capacity of the HCT-116 cells in the absence or presence of avermectin B1a was also investigated. Finally, tubulin polymerization in the presence of avermectin B1a was evaluated. Avermectin B1a presented anti-proliferative activity with an IC50 value of 30 µM. Avermectin B1a was found to promote tubulin polymerization at 30 µM. In addition, avermectin B1a induced apoptosis in HCT-116 cells and substantially diminished their ability to migrate. Avermectin B1a exhibits significant anti-cancer activity and enhances tubulin polymerization, suggesting that it can be used as a promising microtubule-targeting agent for the development of future anticancer drugs.
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The extracellular matrix (ECM), in which collagen is the most abundant protein, impacts many aspects of tumor physiology, including cellular metabolism and intracellular pH (pHi), as well as the efficacy of chemotherapy. Meanwhile, the role of collagen in differential cell responses to treatment within heterogeneous tumor environments remains poorly investigated. In the present study, we simultaneously monitored the changes in pHi and metabolism in living colorectal cancer cells in vitro upon treatment with a chemotherapeutic combination, FOLFOX (5-fluorouracil, oxaliplatin and leucovorin). The pHi was followed using the new pH-sensitive probe BC-Ga-Ir, working in the mode of phosphorescence lifetime imaging (PLIM), and metabolism was assessed from the autofluorescence of the metabolic cofactor NAD(P)H using fluorescence lifetime imaging (FLIM) with a two-photon laser scanning microscope. To model the ECM, 3D collagen-based hydrogels were used, and comparisons with conventional monolayer cells were made. It was found that FOLFOX treatment caused an early temporal intracellular acidification (reduction in pHi), followed by a shift to more alkaline values, and changed cellular metabolism to a more oxidative state. The presence of unstructured collagen markedly reduced the cytotoxic effects of FOLFOX, and delayed and diminished the pHi and metabolic responses. These results support the observation that collagen is a factor in the heterogeneous response of cancer cells to chemotherapy and a powerful regulator of their metabolic behavior.
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Neoplasias , Fótons , Humanos , Microscopia de Fluorescência , Colágeno , Concentração de Íons de HidrogênioRESUMO
The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity towards other S-adenosyl-L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.
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Antineoplásicos , Neoplasias , Animais , Antineoplásicos/farmacologia , Carbazóis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Metilases de Modificação do DNA/metabolismo , Humanos , Mamíferos/metabolismoRESUMO
The present study was aimed at examining the anti-tumor effects and molecular mechanisms of 2'-fucosyllactose (2'-FL). At the beginning, the viabilities of four types of colon cancer cells were analyzed after exposure to increasing concentrations of 2'-FL, and HCT116 cells were selected as the sensitive ones, which were applied in the further experiments; then, interestingly, 2'-FL (102.35 µM) was found to induce apoptosis of HCT116 cells, which coincides with significant changes in VEGFA/VEGFR2/p-PI3K/p-Akt/cleaved Caspase3 proteins. Next, in a tumor-bearing nude mouse model, HCT116 was chosen as the sensitive cell line, and 5-fluorouracil (5-Fu) was chosen as the positive medicine. It was noteworthy that both 2'-FL group (2.41 ± 0.57 g) and 2'FL/5-Fu group (1.22 ± 0.35 g) had a significantly lower tumor weight compared with the control (3.87 ± 0.79 g), suggesting 2'-FL could inhibit colon cancer. Since 2'-FL reduced the number of new blood vessels and the malignancy of tumors, we confirmed that 2'-FL effectively inhibited HCT116 tumors, and its mechanism was achieved by regulating the VEGFA/VEGFR2/PI3K/Akt/Caspase3 pathway. Moreover, though HE staining and organ index measurement, 2'-FL was validated to alleviate toxic effects on liver and kidney tissue when combining with 5-Fu. In conclusion, 2'-FL had certain anti-tumor and detoxification effects.
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Neoplasias do Colo , Proteínas Proto-Oncogênicas c-akt , Humanos , Camundongos , Animais , Fosfatidilinositol 3-Quinases , Fluoruracila/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Células HCT116 , Apoptose , Neovascularização Patológica , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
Ragi porridge, commonly consumed in South India is made from finger millet and noiyee (broken rice), and it is one of the excellent sources for probiotic bacteria. In vitro assays provided the proof that the probiotic strains isolated from ragi porridge can survive during the intestinal passage. Also, it showed antioxidant activity and antagonistic activity against foodborne pathogens including Shigella flexineri, Staphylococcus aureus, Salmonella typhii and Escherichia coli. Enterococcus faecium Rp1 isolated from ragi porridge was susceptible to vancomycin and showed to cease the progression of HCT116 (colon carcinoma) cell line. Further, Enterococcus faecium was microencapsulated using sodium alginate and aloe vera gel as binding agents and onion extract as a source of prebiotic to perform symbiotic encapsulation. In short, this study concludes that the fermented Ragi porridge is a rich source of probiotics with anti-microbial, antioxidant and antiproliferative property hence can be suggested for improving gut microbiota. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05415-2.
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Novel food-derived anti cancerogenic bioactive peptides were characterized by goat milk pepsin hydrolysate. Pepsin treated casein fraction of goat milk caused an apoptotic cell death on the HCT116 cell lines. These bioactive peptides are encrypted in the protein structure in the inactive form and can become active during gastrointestinal digestion in the body. In this study, the possible therapeutic effect of goat milk-based bioactive peptides on human colorectal cancer cell lines was investigated. Goat milk-derived bioactive peptides were extracted from the casein and whey protein fractions using trypsin, pepsin, and papain enzymes. The bioactive peptides were characterized by the liquid chromatography quadrupole time of flight mass spectrometry. Both enzyme-treated casein and whey fractions were incubated with the HCT116 cell lines, and then the cell cytotoxicity was evaluated using MTT assay. The type of cell death was analyzed by flow cytometry using Annexin V and propidium iodide. Among all applications, the pepsin-treated casein fraction was the highest potential peptides that cause 80.92% apoptotic cell death. In conclusion, pepsin treated casein fraction exhibited antiproliferative activity against HCT116 cells. The bioactive peptides of this fraction can be considered as a potential source for the development of new anti cancerogenic agents.
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Anticarcinógenos/farmacologia , Neoplasias Colorretais/patologia , Leite/química , Peptídeos/farmacologia , Animais , Anticarcinógenos/química , Apoptose/efeitos dos fármacos , Caseínas/química , Caseínas/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida/métodos , Neoplasias Colorretais/tratamento farmacológico , Citometria de Fluxo/métodos , Cabras , Células HCT116 , Humanos , Papaína/metabolismo , Pepsina A/metabolismo , Peptídeos/química , Espectrometria de Massas em Tandem/métodos , Tripsina/metabolismoRESUMO
This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF--5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the (1) induction of cell cycle arrest in the S phase and (2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal-epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células CACO-2 , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fluoruracila/farmacologia , Células HCT116 , Humanos , Polissacarídeos/farmacologiaRESUMO
Colon carcinogenesis is ranked second globally among human diseases after cardiovascular failures. Bee venom (BV) has been shown to possess in vitro anticancer effects against several types of cancer cells. The two main biopeptides of Apis mellifera BV, namely, melittin (MEL) and phospholipase A2 (PLA2), are suspected to be the biomolecules responsible for the anticancer activity. The present work aims to evaluate the cytotoxic effect of the A. mellifera venom on human colon carcinoma cells (HCT116), and to assess the synergistic effect of MEL and PLA2 on these cells. After analyzing, through high-pressure liquid chromatography, the proportions of MEL and PLA2 on BV, we have established a cell viability assay to evaluate the effect of BV, MEL, PLA2, and a mixture of MEL and PLA2 on the HCT116 cells. Results obtained showed a strong cytotoxicity effect induced by the A. mellifera venom and to a lower extent MEL or PLA2 alone. Remarkably, when MEL and PLA2 were added together, their cytotoxic effect was greatly improved, suggesting a synergistic activity on HCT116 cells. These findings confirm the cytotoxic effect of the A. mellifera venom and highlight the presence of synergistic potential activities between MEL and PLA2, possibly inducing membrane disruption of HCT116 cancer cells. Altogether, these results could serve as a basis for the development of new anticancer treatments.
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Abelhas/química , Neoplasias do Colo/patologia , Meliteno/farmacologia , Fosfolipases A2/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Sinergismo Farmacológico , Células HCT116 , HumanosRESUMO
The urea cycle (UC) removes the excess nitrogen and ammonia generated by nitrogen-containing compound composites or protein breakdown in the human body. Research has shown that changes in UC enzymes are not only related to tumorigenesis and tumor development but also associated with poor survival in hepatocellular, breast, and colorectal cancers (CRC), etc. Cytoplasmic ornithine, the intermediate product of the urea cycle, is a specific substrate for ornithine decarboxylase (ODC, also known as ODC1) for the production of putrescine and is required for tumor growth. Polyamines (spermidine, spermine, and their precursor putrescine) play central roles in more than half of the steps of colorectal tumorigenesis. Given the close connection between polyamines and cancer, the regulation of polyamine metabolic pathways has attracted attention regarding the mechanisms of action of chemical drugs used to prevent CRC, as the drug most widely used for treating type 2 diabetes (T2D), metformin (Met) exhibits antitumor activity against a variety of cancer cells, with a vaguely defined mechanism. In addition, the influence of metformin on the UC and putrescine generation in colorectal cancer has remained unclear. In our study, we investigated the effect of metformin on the UC and putrescine generation of CRC in vivo and in vitro and elucidated the underlying mechanisms. In nude mice bearing HCT116 tumor xenografts, the administration of metformin inhibited tumor growth without affecting body weight. In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC. The putrescine levels in both HCT116 xenografts and HCT116 cells decreased after metformin treatment. These results demonstrate that metformin inhibited CRC cell proliferation via activating AMPK/p53 and that there was an association between metformin, urea cycle inhibition and a reduction in putrescine generation.
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Neoplasias Colorretais/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Metformina/farmacologia , Putrescina/biossíntese , Ureia/metabolismo , Animais , Biomarcadores , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Expressão Gênica , Perfilação da Expressão Gênica , Xenoenxertos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
PURPOSE: The aim of this study was to determine the biological function of pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1), a recently discovered protein, in colon cancer cell line HCT116. METHODS: The small interfering RNA (siRNA) was designed rationally on the basis of the target sequence against PYROXD1. Relative PYROXD1 mRNA levels were measured by a quantitative real-time polymerase chain reaction. Flow cytometry was performed to monitor tumor cells proliferation and apoptosis after siRNA transfection. RESULTS: Knockdown of PYROXD1 arrested the cell cycle, and induced late apoptosis in colon cancer cell line HCT116 DISCUSSION: Taken together, these results revealed the critical roles of PYROXD1 in regulating cell cycle and apoptosis and possibly will signify its therapeutic potential for targeting colorectal cancer models.
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Neoplasias do Colo/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , RNA Interferente Pequeno/metabolismo , Anexina A6/genética , Anexina A6/metabolismo , Apoptose/genética , Apoptose/fisiologia , Ciclo Celular/genética , Ciclo Celular/fisiologia , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/fisiologia , Neoplasias do Colo/genética , Citometria de Fluxo , Células HCT116 , Humanos , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor studies were carried out on the U937, HCT-116, PC3, MCF-7, A549, Ð562, NCI-H929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 (IC50â¯=â¯0.59⯱â¯0.27⯵M) was observed to be 11 times more active than PPA (IC50â¯=â¯6.5⯱â¯0.30⯵M) towards the NCI-H929 cell line, with a therapeutic index of 18. Compound 6 was determined to be over half and 16 times more active than etoposide towards the NCI-H929 (IC50â¯=â¯0.9⯱â¯0.05⯵M) and A549 (IC50â¯=â¯100⯱â¯7.0⯵M) cell lines, respectively.
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Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
This study aimed to investigate the characterization of zinc oxide nanoparticles (ZnONPs) produced from Cucurbita pepo L. (pumpkin seeds) and their selective cytotoxic effectiveness on human colon cancer cells (HCT 116) and African Green Monkey Kidney, Vero cells. The study also investigated the antioxidant activity of ZnONPs. The study also examined ZnONPs' antioxidant properties. This was motivated by the limited research on the comparative cytotoxic effects of ZnO NPs on normal and HCT116 cells. The ZnO NPs were characterized using Fourier-transform infrared spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Transmission Electron Microscope/Selected Area Electron Diffraction (TEM/SAED), and Scanning Electron Microscope-Energy Dispersive X-ray (SEM-EDX) for determination of chemical fingerprinting, heat stability, size, and morphology of the elements, respectively. Based on the results, ZnO NPs from pumpkins were found to be less than 5 µm and agglomerates in nature. Furthermore, the ZnO NPs fingerprinting and SEM-EDX element analysis were similar to previous literature, suggesting the sample was proven as ZnO NPs. The ZnO NPs also stable at a temperature of 380°C indicating that the green material is quite robust at 60-400°C. The cell viability of Vero cells and HCT 116 cell line were measured at two different time points (24 and 48 h) to assess the cytotoxicity effects of ZnO NP on these cells using AlamarBlue assay. Cytotoxic results have shown that ZnO NPs did not inhibit Vero cells but were slightly toxic to cancer cells, with a dose-response curve IC50 = ~409.7 µg/mL. This green synthesis of ZnO NPs was found to be non-toxic to normal cells but has a slight cytotoxicity effect on HCT 116 cells. A theoretical study used molecular docking to investigate nanoparticle interaction with cyclin-dependent kinase 2 (CDK2), exploring its mechanism in inhibiting CDK2's role in cancer. Further study should be carried out to determine suitable concentrations for cytotoxicity studies. Additionally, DPPH has a significant antioxidant capacity, with an IC50 of 142.857 µg/mL. RESEARCH HIGHLIGHTS: Pumpkin seed extracts facilitated a rapid, high-yielding, and environmentally friendly synthesis of ZnO nanoparticles. Spectrophotometric analysis was used to investigate the optical properties, scalability, size, shape, dispersity, and stability of ZnO NPs. The cytotoxicity of ZnO NPs on Vero and HCT 116 cells was assessed, showing no inhibition of Vero cells and cytotoxicity of cancer cells. The DPPH assay was also used to investigate the antioxidant potential of biogenic nanoparticles. A molecular docking study was performed to investigate the interaction of ZnO NPs with CDK2 and to explore the mechanism by which they inhibit CDK2's role in cancer.
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Antineoplásicos , Cucurbita , Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Humanos , Animais , Chlorocebus aethiops , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antioxidantes/farmacologia , Cucurbita/metabolismo , Simulação de Acoplamento Molecular , Células Vero , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Nanopartículas/química , Antineoplásicos/farmacologia , Sementes/química , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Difração de Raios XRESUMO
Background: Sodium butyrate (NaBu) is a short-chain fatty acid; it is one of the histone deacetylase inhibitors, which can alter both genetic and epigenetic expressions. The present study aimed to elucidate the effect of Na-Bu on the expression of miR-21, miR-143, and miR-145 in human colorectal cancer HCT-116 cell lines. Methods: This study was done in Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. HCT-116 cell line was treated with diverse concentrations of NaBu (6.25 mM to 200 mM) at 24, 48, and 72 h. MTT assay was used for assessing the cytotoxicity. Quantitative Real-Time-PCR was performed to investigate the gene expression of miR-21, miR-143, and miR-145. Results: IC50 values were evaluated by MTT assay. IC50 for HCT-116 was 50 mM, 12.5 mM, and 6.25 mM for 24, 48, and 72 h of incubation, respectively. According to the Real-Time-PCR results, 50 mM NaBu after 24 h caused a significant up-regulation in the expression of the miR-21, miR-143, and miR-145 (P<0.05). In 48 h, incubation, 12.5 mM NaBu caused a significant up-regulation in the expression of the miR-21, miR-143, and miR-145 (P<0.05). In treated cells with 6.25 mM NaBu after 72 h of incubation caused a significant up-regulation in the expression of the miR-21, miR-143, and miR-145 compared with untreated cells (P<0.05). Conclusion: The upregulation of miR-21, miR-143, and miR-145 expression are mediated by transcriptional regulation and the activation of this miR promoter is modulated by histone acetylation. The employment of NaBu may represent a promising approach for improving HDACi drug-based therapies for colon cancers.
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BACKGROUND: Propolis is a complex resinous sticky substance that honeybees collect from buds and exudates of various plants. Owing to its versatile biological and pharmacological activities, propolis is widely used in medicines, cosmetics and foods. The aim of this study was to evaluate the cytotoxic and antioxidative effects of various ethanolic extracts of propolis (EEPs) on human colon cancer cell line HCT-116 and compare them with their composition determined by HPLC-DAD. RESULTS: The most abundant flavonoids in all samples were chrysin, pinocembrin and galangin (12.697-40.811 µg mg⻹), while the main phenolic acids were caffeic acid, ferulic acid and isoferulic acid. Dose- and time-dependent inhibition of growth of HCT-116 cells was observed for all propolis samples, with IC50 values ranging from 26.33 to 143.09 µg mL⻹. Differences in cytotoxic activity of propolis samples were associated with differences in their composition. All EEP samples reduced both superoxide anion radical and nitrite levels and also had strong DPPH-scavenging activity. CONCLUSION: All tested propolis samples had pronounced cytotoxic and antioxidative activities.
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Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Própole/química , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais/análise , Etanol/química , Flavonoides/análise , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Células HCT116 , Humanos , Concentração Inibidora 50 , Fenóis/análise , Sérvia , Solventes/química , Espectrofotometria Ultravioleta , Fatores de TempoRESUMO
Scientists are finding the most effective chemotherapeutic agents for the treatment of cancer. In the present study, we evaluated the anticancer mechanism of DPPG, a derivative of DAPG (2,4-diacetylphloroglucinol), for the first time. DPPG and DAPG inhibited 83 and 59% of human colorectal cancer HCT116 cell growth at 40.0 µg/ml, and 74 and 57% of human lung cancer A549 cell growth at 10.0 µg/ml concentrations respectively. Furthermore, DPPG and DAPG inhibited 97 and 73% colony formation of the HCT116 cells at 20.0 µg/ml concentration. DPPG and DAPG induced apoptosis in the HCT116 and A549 cells that was confirmed by Hoechst 33342 and FITC-annexin V staining. This result also revealed that ROS generated in both the HCT116 and A549 cells after treatment with DPPG. However, no ROS production was observed in HCT116 and A549 cells after treatment with DAPG. Both DAPG and DPPG significantly increased the CASP3 protein expression that was detected by staining the cells with the super-view 488-CASP3 substrate. Expression of WNT1 gene was eliminated in DPPG and DAPG treated HCT116. Expression of MAPK1 gene was entirely abolished in DPPG treated cells, whereas a significant decrease was observed for DAPG. An intense band of CASP8 gene product was observed agarose gel for DPPG treated HCT116 cells than DAPG. Molecular docking simulation showed the high binding affinities (≥ 6.5 kcal/mol) of DPPG and DAPG with target proteins WNT1, MAPK1, CASP8, and CASP3 in HCT116 cells. This manuscript demonstrated that DAPG and DPPG inhibited lung and colorectal cancer cells by inducing apoptosis. DAPG and DPPG inhibited A549 and HCT116 cells growth by inducing apoptosis.
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Apoptose , Neoplasias Colorretais , Humanos , Linhagem Celular Tumoral , Caspase 3 , Simulação de Acoplamento Molecular , Proliferação de Células , Pulmão , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Células HCT116RESUMO
Colorectal cancer is the most common malignant cancer in developing countries. Canarium odontophyllum, also known as "Dabai" or "Borneo Olive" is among the natural plants that can potentially be used as an anticancer agent. This study aims to determine the antiproliferative activities and cytotoxicity effects of acetone extract from C. odontophyllum stem bark against human colorectal cancer cell lines HCT 116 and HT 29. Acetone extract of C. odontophyllum stem bark exerted a significant cytotoxic effect on HCT 116 and HT 29 cells determined by MTT assay at the concentration of 12.5 µg/mL to 200 µg/mL for 24, 48, and 72 hours treatment. It was found that acetone extract of C. odontophyllum stem bark inhibited proliferation of HCT 116 with an IC50 value of 184.93 ± .0 µg/mL, 61.24 ± .1 µg/mL, 79.98 ± .029 for 24, 48 and 72 hours respectively. The findings also showed that acetone extract of C. odontophyllum stem bark revealed a lower inhibitory effect against HT-29 with an IC50 value of more than 200 µg/mL for 24, 48 and 72 hours. However, acetone extract of C. odontophyllum stem bark at similar concentrations and time points did not show any cytotoxic effect to normal colorectal fibroblast cell CCD18-Co. In conclusion, the acetone extract of C. odontophyllum stem bark exhibited more sensitivity against HCT 116 than HT 29. Its antiproliferative ability towards HCT 116 and HT 29 cells provides insight that this extract may serve as an anticancer agent against colorectal cancer.
RESUMO
PURPOSE: The therapeutic use of herbal medicines for the diseases, including cancer, is increasing due to their lower side effects. The present research evaluated the effect of Peucedanum chenur chloroformic extract (PCCE) on cell proliferation against HCT-116 human colorectal cancer cell line. METHODS: The cytotoxic effect of PCCE was evaluated by MTT assay. The activity of the Wnt/B-catenin pathway was assayed through measuring the expression of miR-135b, miR-21, and APC genes by real-time PCR. The flow cytometry and scratch tests were used to study the cell cycle and cell migration, respectively. Also, the antioxidant activity of PCCE was measured by DPPH and iron-chelating tests. RESULTS: The results showed the downregulation of miR-135b and miR-21 and overexpression of the APC gene. Furthermore, PCCE decreased the free radicals, cell migration, and cell proliferation. The antioxidant activity of PCCE was confirmed by standard tests. CONCLUSION: Altogether, our findings suggest that purified compounds of PCCE could be developed as a potent chemo-preventive drug for the treatment of CRC.
Assuntos
Neoplasias Colorretais , MicroRNAs , Proteína da Polipose Adenomatosa do Colo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/genética , Clorofórmio/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Genes APC , Humanos , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Gold nanoparticles (AuNPs) modified with four organoselenium compounds, i.e., 4-selenocyanatoaniline (compound 1), 4,4'-diselanediyldianiline (compound 2), N-(4-selenocyanatophenyl)cinnamamide (compound 3), and N-(3-selenocyanatopropyl)cinnamamide (compound 4), were synthesized following two different approaches: direct conjugation and non-covalent immobilization onto hydrophilic and non-cytotoxic AuNPs functionalized with 3-mercapto-1-propanesulfonate (3MPS). Both free compounds and AuNPs-based systems were characterized via UV-Vis, FTIR NMR, mass spectrometry, and SR-XPS to assess their optical and structural properties. Size and colloidal stability were evaluated by DLS and ζ-potential measurements, whereas morphology at solid-state was evaluated by atomic force (AFM) and scanning electron (FESEM) microscopies. AuNPs synthesized through chemical reduction method in presence of Se-based compounds as functionalizing agents allowed the formation of aggregated NPs with little to no solubility in aqueous media. To improve their hydrophilicity and stability mixed AuNPs-3MPS-1 were synthesized. Besides, Se-loaded AuNPs-3MPS revealed to be the most suitable systems for biological studies in terms of size and colloidal stability. Selenium derivatives and AuNPs were tested in vitro via MTT assay against PC-3 (prostatic adenocarcinoma) and HCT-116 (colorectal carcinoma) cell lines. Compared to free compounds, direct functionalization onto AuNPs with formation of Au-Se covalent bond led to non-cytotoxic systems in the concentration range explored (0-100 µg/mL), whereas immobilization on AuNPs-3MPS improved the cytotoxicity of compounds 1, 3, and 4. Selective anticancer response against HCT-116 cells was obtained by AuNPs-3MPS-1. These results demonstrated that AuNPs can be used as a platform to tune the in vitro biological activity of organoselenium compounds.
Assuntos
Nanopartículas Metálicas , Neoplasias , Humanos , Ouro/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Cinamatos , Neoplasias/tratamento farmacológicoRESUMO
Chemotherapy is a general treatment procedure for cancer. The diversity in cancer incidence and the failure of therapy due to chemoresistance lead to increased cancer-related deaths. Therefore, new drugs with fewer secondary complications targeting diverse pathways are the need of the hour. Geranyl isovalerate (GIV), one of the active ingredients of ethyl acetate fraction of Argyreia nervosa is routinely used as a food flavoring agent. In this study, we found that GIV also exhibits anticancer activity when tested against the HCT116 cell line. It influenced the viability of the cells in a dose- and time-dependent manner. We examined whether GIV could induce oxidative stress and affect the mitochondrial membrane potential, thereby leading to apoptosis induction. Moreover, GIV could suppress the expression of antiapoptotic genes, such as BCl2 and PARP, and induce the expression of proapoptotic genes, such as Caspase 3 and 9. This is the first study demonstrating the anticancer activity of GIV and providing evidence for its mechanism of action. In conclusion, this study proposes GIV as a potential lead or supplementary molecule in treating and preventing colorectal cancer (CRC). Based on our findings, we conclude that GIV may be a viable lead or supplementary molecule for treating and preventing CRC.