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1.
Anticancer Agents Med Chem ; 23(8): 967-978, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36305129

RESUMO

BACKGROUND: The success of drug treatment of colon cancer (CC), which is in the top three in terms of incidence and mortality among all cancers, is adversely affected by reasons, such as severe side effects and chemoresistance. Clinical, epidemiological and experimental studies have indicated the need for developing new alternative drugs for the treatment of CC. Plants are an important source of traditional medicines that have proven to be highly beneficial for the treatment of CC. AIM: In this study, we aimed to reveal the antioxidant properties and anti-carcinogenic activity of Salsola grandis methanol extract (SGME) on HT-29. METHODS: For this purpose, we used spectrophotometric methods to determine the antioxidant properties of SGME and LC-MS/MS analysis to measure the phenolic acid composition. We applied 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, the thiazolyl blue (MTT) method, to evaluate its effects on cell viability and ELISA assay, realtime PCR, and western blot method to reveal its effects on apoptosis. RESULTS: Spectrophotometric analyzes showed that SGME has the highest phenolic acid content, inhibits plasma lipid peroxidation and shows chelating activity and radical scavenging activity. Gene and protein expression analysis revealed the effects of SGME treatment on apoptosis genes/proteins. CONCLUSION: These findings showed that SGME has anticarcinogenic activity on CC due to its antioxidant, cell viability- suppressing and apoptosis-inducing properties.


Assuntos
Neoplasias do Colo , Salsola , Humanos , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Neoplasias do Colo/tratamento farmacológico
2.
Toxicol In Vitro ; 82: 105368, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35476923

RESUMO

The aim of the present study is to discover a bacterial pigment providing protection and prevention of neurological damage and cancer development, which can have a role as a non-synthetic food additive in the food industry as well as an active drug ingredient of anticancer drugs and pharmaceuticals for neural injury. Within this scope, Serratia marcescens MB703 strain was used to produce prodigiosin. Characterization of the prodigiosin was carried out using UV-VIS, and FT-IR. In addition, its inhibitory action on AChE and antioxidant activities were determined. The cytotoxic, genotoxic and antigenotoxic activities of the prodigiosin as well as its antiproliferative activities were detected. It was determined that the maximum production of the prodigiosin (72 mg/L). The prodigiosin was found to cause no significant difference in its inhibitory effect on AChE. The prodigiosin was found effective on all antioxidant parameters tested. The IC50 values of the prodigiosin on SK-MEL-30 and HT-29 cells were calculated as 70 and 47 µM, respectively. This IC50 values of the prodigiosin showed no cytotoxic effect on L929 cells. Prodigiosin did not have genotoxic effect alone and also seem to decrease DNA damage induced by H2O2 in L929 cells. The findings of in vitro experimental studies suggest that using the prodigiosin pigment as a drug candidate for cancer and neurodegenerative disease therapy is both effective and safe.


Assuntos
Antineoplásicos , Doenças Neurodegenerativas , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Humanos , Peróxido de Hidrogênio , Prodigiosina/farmacologia , Serratia marcescens/genética , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Anticancer Agents Med Chem ; 22(9): 1769-1779, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34503424

RESUMO

BACKGROUND: In the treatment of Colorectal Cancer (CRC), the search for new antineoplastic drugs with fewer side effects and more effectiveness continues. A significant part of these pursuits and efforts focus on medicinal herbs and plant components derived from these plants. A. ketenoglui is one of these medicinal plants, and its anticancer potential has never been studied before. METHODS: The phenolic and flavonoid content, and antioxidant activity of A. ketenoglui extracts were determined. The phytochemical profiling and quantification analysis of major components were performed by HPLC-ESI-Q-TOF-MS. Cytotoxicity, proliferation, apoptosis and cell cycle were evaluated to reveal the anticancer activity of the extract on CRC cells (HCT 116 and HT-29). The determined anticancer activity was confirmed by mRNA (RT-qPCR) and protein (Western blotting) analyzes. RESULTS: A. ketenoglui methanol extract was found to have high phenolic (281.89±0.23) and flavonoid (33.80±0.15) content and antioxidant activity (IC50 40.03±0.38). According to the XTT assay, the extract has strong cytotoxic activity (IC50 350 µM in HCT 116 and IC50 263 µM in HT-29 cell line). The compounds most commonly found in the plant are, in descending order, chlorogenic acid, apigenin, genistin, baicalin, eupatorin, casticin, and luteolin. In flowcytometric analysis, the extract was found to induce greater apoptosis and cell cycle arrest in both cell lines than in both control and positive control (casticin). According to the results of the mRNA expression analysis, the extract treatment upregulated the expression of the critical genes of the cell cycle and apoptosis, such as p53, p21, caspase-3, and caspase-9. In protein expression analysis, an increase in caspase-3 and p53 expression was observed in both cell lines treated with the extract. In addition, caspase-9 expression was increased in HT-29 cells. CONCLUSION: The findings show that A. ketenoglui has an anticancer potential by inducing apoptosis and arresting the cancer cell cycle and may be promising for CRC therapy. This potential of the plant is realized through the synergistic effects of its newly identified components.


Assuntos
Achillea , Neoplasias Colorretais , Plantas Medicinais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose , Caspase 3 , Caspase 9 , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/química , RNA Mensageiro , Proteína Supressora de Tumor p53
4.
Sci Rep ; 10(1): 8124, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415207

RESUMO

Alzheimer's disease (AD) is a disease characterized by cerebral neuronal degeneration and loss in a progressive manner. Amyloid beta (Aß) in the brain is toxic to neurons, being a main risk factor for initiation and continuation of cognitive deterioration in AD. Neurotoxicity of Aß origin is also linked to oxidative stress characterized by excessive lipid peroxidation, protein oxidation, changes in antioxidant systems, and cerebral DNA damage in AD. Furthermore, Aß can induce oxidative neuronal cell death by a mitochondrial dysfunction. Cellular injury caused by oxidative stress can be possibly prevented by boosting or promoting bodily oxidative defense system by supplying antioxidants in diet or as medications. However, most synthetic antioxidants are found to have cytotoxicity, which prevents their safe use, and limits their administration. For this reason, more attention has been paid to the natural non-toxic antioxidants. One of the most promising groups of non-toxic antioxidative compounds is thought to be polysaccharides. This study investigated the characterization and protective action exerted by exopolysaccharides (EPSs) originated from Lactobacillus delbrueckii ssp. bulgaricus B3 and Lactobacillus plantarum GD2 to protect from apoptotic activity exerted by Aß1-42 among SH-SY5Y cells. We characterized EPSs by elemental analysis, FTIR, AFM, SEM, and XRD. The antioxidant effects of EPSs were determined by the DPPH free radical scavenging activity, hydroxyl radical scavenging activity, metal ion chelating activity, lipid peroxidation inhibitory activity, and superoxide anion scavenging activity method. The protective effects of EPSs were determined by flow cytometry and RT-PCR. Mannose ratio, molecular weight, functional groups, surface morphology, and amorphous character structure of EPSs are thought to play a role in the protective effect of EPSs. EPSs reduced apoptotic activity of Aß1-42 in addition to their depolarizing effect on mitochondrial membrane potential in concentration-dependent manner. These observations contribute the inclusion of EPSs among the therapeutic options used to manage various neurological disorders in the traditional medicine in a scientific manner, indicating that EPSs may be promising natural chemical constituents that need advanced research and development for pharmacological therapy of AD.


Assuntos
Peptídeos beta-Amiloides/efeitos adversos , Antioxidantes/farmacologia , Apoptose , Lactobacillales/metabolismo , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/efeitos adversos , Polissacarídeos Bacterianos/farmacologia , Humanos , Peroxidação de Lipídeos , Potencial da Membrana Mitocondrial , Neuroblastoma/induzido quimicamente , Neuroblastoma/patologia , Oxirredução , Estresse Oxidativo , Células Tumorais Cultivadas
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