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1.
Int J Mol Sci ; 25(16)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39201395

RESUMEN

Gliomas account for 24% of all the primary brain and Central Nervous System (CNS) tumors. These tumors are diverse in cellular origin, genetic profile, and morphology but collectively have one of the most dismal prognoses of all cancers. Work is constantly underway to discover a new effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound-a photosensitizer (PS)-which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating the activation processes leading to the formation of reactive oxygen species and the selective destruction of inappropriate cells. Research focusing on the effective use of PDT in glioma therapy is already underway with promising results. In our work, we provide detailed insights into the molecular changes in glioma after photodynamic therapy. We describe a number of molecules that may contribute to the resistance of glioma cells to PDT, such as the adenosine triphosphate (ATP)-binding cassette efflux transporter G2, glutathione, ferrochelatase, heme oxygenase, and hypoxia-inducible factor 1. We identify molecular targets that can be used to improve the photosensitizer delivery to glioma cells, such as the epithelial growth factor receptor, neuropilin-1, low-density lipoprotein receptor, and neuropeptide Y receptors. We note that PDT can increase the expression of some molecules that reduce the effectiveness of therapy, such as Vascular endothelial growth factor (VEGF), glutamate, and nitric oxide. However, the scientific literature lacks clear data on the effects of PDT on many of the molecules described, and the available reports are often contradictory. In our work, we highlight the gaps in this knowledge and point to directions for further research that may enhance the efficacy of PDT in the treatment of glioma.


Asunto(s)
Neoplasias Encefálicas , Resistencia a Antineoplásicos , Glioma , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Glioma/tratamiento farmacológico , Glioma/metabolismo , Glioma/patología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Especies Reactivas de Oxígeno/metabolismo
2.
Molecules ; 28(23)2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38067567

RESUMEN

Inflammation plays an important role in the immune defense against injury and infection agents. However, the inflammatory chronic process may lead to neurodegenerative diseases, atherosclerosis, inflammatory bowel diseases, or cancer. Flavanones present in citrus fruits exhibit biological activities, including anti-oxidative and anti-inflammatory properties. The beneficial effects of flavanones have been found based on in vitro cell cultures and animal studies. A suitable in vitro model for studying the inflammatory process are macrophages (RAW264.7 cell line) because, after stimulation using lipopolysaccharide (LPS), they release inflammatory cytokines involved in the immune response. We determined the nitrite concentration in the macrophage cell culture and detected ROS using chemiluminescence. Additionally, we measured the production of selected cytokines using the Bio-Plex Magnetic Luminex Assay and the Bio-PlexTM 200 System. For the first time, we have shown that methyl derivatives of flavanone inhibit NO and chemiluminescence generated via LPS-stimulated macrophages. Moreover, the tested compounds at 1-20 µM dose-dependently modulate proinflammatory cytokine production (IL-1ß, IL-6, IL-12p40, IL-12p70, and TNF-α) in stimulated RAW264.7 cells. The 2'-methylflavanone (5B) and the 3'-methylflavanone (6B) possess the strongest anti-inflammatory activity among all the tested flavanone derivatives. These compounds reduce the concentration of IL-6, IL-12p40, and IL12p70 compared to the core flavanone structure. Moreover, 2'-methylflavanone reduces TNF-α, and 3'-methylflavanone reduces IL-1ß secreted by RAW264.7 cells.


Asunto(s)
Flavanonas , Factor de Necrosis Tumoral alfa , Animales , Factor de Necrosis Tumoral alfa/metabolismo , Subunidad p40 de la Interleucina-12 , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Flavanonas/farmacología , Flavanonas/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Óxido Nítrico/metabolismo
3.
Mediators Inflamm ; 2018: 7161346, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30013452

RESUMEN

The pathogenesis of chronic venous disease (CVD) remains unclear, but lately inflammation is suggested to have an important role in its development. This study is aimed at assessing cytokines released by lymphocytes in patients with great saphenous vein (GSV) incompetence. In 34 patients exhibiting oscillatory flow (reflux) in GSV, blood was derived from the cubital vein and from the incompetent sapheno-femoral junction. In 12 healthy controls, blood was derived from the cubital vein. Lymphocyte culture with and without stimulation by phytohemagglutinin (PHA) was performed. Interleukins (IL) 1ß, 2, 4, 10, 12 (p70), and 17A; interleukin 1 receptor α (IL-1ra); tumor necrosis factor-α (TNF-α); interferon-gamma (IFN-γ); and RANTES were assessed in culture supernatants by the Bio-Plex assay. In both stimulated and unstimulated samples, in the examined group, IL-1ß and IFN-γ had higher concentrations and RANTES had lower concentrations when compared to those in the control group. In the examined group, IL-4 and IL-17A had higher concentrations without stimulation and TNF-α had higher concentrations with stimulation. The GSV samples had higher IL-2, IL-4, IL-12 (p70), and IFN-γ concentrations without stimulation and lower IL-2 and TNF-α concentrations with stimulation when compared to those of the upper limb in the examined group. These observations indicate that the oscillatory flow present in incompetent veins causes changes in the cytokine production by lymphocytes, promoting a proinflammatory profile. However, the relations between immunological cells, cytokines, and the endothelium require more insight.


Asunto(s)
Citocinas/metabolismo , Linfocitos/metabolismo , Vena Safena/patología , Adulto , Anciano , Femenino , Voluntarios Sanos , Humanos , Sistema Inmunológico , Inflamación , Interferón gamma/metabolismo , Linfocitos/citología , Masculino , Persona de Mediana Edad , Oscilometría , Fitohemaglutininas/química , Factor de Necrosis Tumoral alfa/metabolismo , Adulto Joven
4.
Int J Mol Sci ; 18(8)2017 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-28758908

RESUMEN

Numerous data suggest that an increase of cancer stem cells (CSCs) in tumor mass can be the reason for failure of conventional therapies because of their resistance. CD44+/CD24- cells are a putative cancer stem cells subpopulation in prostate cancer. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an activator of apoptosis in tumor cells. However, some tumors are TRAIL-resistant. Cancer cells can be re-sensitized to TRAIL induced apoptosis by a combination of TRAIL and taxanes. The aim of this work was to analyze the enhancement of the anticancer effect of TRAIL by paclitaxel, cabazitaxel and docetaxel in the whole population of PC3 and DU145 prostate cancer cells, but also in CD44+/CD24- prostate cancer stem cells. We examined the apoptotic effect of TRAIL and taxanes using flow cytometry and Annexin-V-PE staining. The co-treatment with taxanes and TRAIL enhanced significantly the apoptosis in CD44+/CD24- cells only in PC3 cell line but not in DU145 cells. We discovered also that taxanes can increase the expression of death receptor TRAIL-R2 in PC3 prostate cancer cells. The results of our study show that treatment with paclitaxel, cabazitaxel and docetaxel is able to enhance the apoptosis induced by TRAIL even in prostate cancer stem cells.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Neoplasias de la Próstata/metabolismo , Humanos , Masculino , Células Madre Neoplásicas/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología
5.
Int J Mol Sci ; 18(6)2017 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-28587286

RESUMEN

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) was identified as a powerful activator of apoptosis in tumor cells and one of the most promising candidates for cancer therapy with no toxicity against normal tissues. However, many tumor cells are resistant to TRAIL-induced apoptosis. The aim of this work was to analyze the improvement of the anticancer effect of rhsTRAIL (recombinant human soluble TRAIL) by nine flavones: 5-Hydroxyflavone, 6-Hydroxyflavone, 7-Hydroxyflavone and their new synthetic derivatives 5-acetoxyflavone, 5-butyryloxyflavone, 6-acetoxyflavone, 6-butyryloxyflavone, 7-acetoxyflavone and 7-butyryloxyflavone. We examined the cytotoxic and apoptotic effects of rhsTRAIL enhanced by novel structurally-related flavones on SW480 and SW620 colon cancer cells using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, the lactate dehydrogenase assay and annexin V-FITC fluorescence staining. We observed a slight difference in the activities of the flavones that was dependent on their chemical structure. Our study indicates that all nine flavones significantly augment cell death by rhsTRAIL (cytotoxicity range 36.8 ± 1.7%-91.4 ± 1.7%; apoptosis increase of 33.0 ± 0.7%-78.5 ± 0.9%). Our study demonstrates the potential use of tested flavones in TRAIL-based anticancer therapy and prevention.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Flavonas/química , Flavonas/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Línea Celular Tumoral , Neoplasias del Colon/patología , Sinergismo Farmacológico , Humanos , Proteínas Recombinantes/farmacología
6.
Molecules ; 22(11)2017 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-29137160

RESUMEN

The study was based on the use of a toothpaste with antiphlogistic activity, containing Australian Melaleuca alternifolia oil (tea tree oil-TTO) and ethanolic extract of Polish propolis (EEP). Fifty-one patients with varying conditions of the gingiva were divided into two groups. The study group received the toothpaste with TTO and EEP, while the control group received the same toothpaste but without TTO and EEP. Approximal plaque index (API), simplified oral hygiene index (OHI-s) and modified sulcus bleeding index (mSBI) were assessed in three subsequent stages. During each examination, swabs were employed for microbiological inoculation. During the period of use of toothpastes with TTO and EEP, a significant reduction of the API was observed, as assessed upon the control visit after 7 days and after 28 days, compared to baseline. A statistically significant reduction of mSBI was observed after 7 and 28 days of using the toothpaste with TTO and EEP, as compared to the value upon the initial visit. Statistically significant differences in the OHI-s value were observed in the study group, which was using the active toothpaste. The use of a toothpaste containing TTO and EEP helps to maintain microbiome balance. The observed stabilisation of bacterial microflora confirms the beneficial activity of toothpaste containing EEP and TTO compared to the control group, where the lack of these substances contributed to the emergence of qualitative and quantitative changes in oral microbiome.


Asunto(s)
Microbiota , Boca/microbiología , Higiene Bucal , Própolis/análisis , Aceite de Árbol de Té/análisis , Pastas de Dientes/análisis , Placa Dental/microbiología , Femenino , Humanos , Masculino
7.
Int J Mol Sci ; 17(6)2016 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-27338375

RESUMEN

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an endogenous ligand, which plays role in immune surveillance and anti-tumor immunity. It has ability to selectively kill tumor cells showing no toxicity to normal cells. We tested the apoptotic and cytotoxic activities of xanthohumol, a prenylated chalcone found in Humulus lupulus on androgen-sensitive human prostate adenocarcinoma cells (LNCaP) in combination with TRAIL. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction assay (MTT) and lactate dehydrogenase assay (LDH). The expression of death receptors (DR4/TRAIL-R1 and DR5/TRAIL-R2) and apoptosis were detected using flow cytometry. We examined mitochondrial membrane potential (ΔΨm) by DePsipher reagent using fluorescence microscopy. The intracellular expression of proteins was evaluated by Western blotting. Our study showed that xanthohumol enhanced cytotoxic and apoptotic effects of TRAIL. The tested compounds activated caspases-3, -8, -9, Bid, and increased the expression of Bax. They also decreased expression of Bcl-xL and decreased mitochondrial membrane potential, while the expression of death receptors was not changed. The findings suggest that xanthohumol is a compound of potential use in chemoprevention of prostate cancer due to its sensitization of cancer cells to TRAIL-mediated apoptosis.


Asunto(s)
Adenocarcinoma/metabolismo , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Flavonoides/toxicidad , Extractos Vegetales/toxicidad , Propiofenonas/toxicidad , Neoplasias de la Próstata/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Flavonoides/farmacología , Humanos , Humulus/química , Ligandos , Masculino , Extractos Vegetales/farmacología , Propiofenonas/farmacología , Receptores de Muerte Celular/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
8.
Int J Mol Sci ; 16(11): 27433-49, 2015 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-26593898

RESUMEN

Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.


Asunto(s)
Células Madre Neoplásicas/metabolismo , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/metabolismo , Animales , Biomarcadores , Transformación Celular Neoplásica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Transducción de Señal , Nicho de Células Madre
9.
Molecules ; 20(1): 900-12, 2015 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-25580686

RESUMEN

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptors (TRAIL-R) are an important factor of apoptosis in cancer cells. There are no data about the effect of flavonols on the receptor expression on a surface of macrophage like cells. In this study, the expression level of TRAIL-R1 on murine RAW264.7 macrophages in the presence of selected flavonols: galangin, kaempferol, kaempferide and quercetin, which differ from their phenyl ring substituents, were studied. The expression of TRAIL-R1 death receptors on non-stimulated and lipopolysaccharide (LPS)-stimulated macrophages was determined using flow cytometry. The results suggested that compounds being tested can modulate TRAIL-R1 expression and can enhance TRAIL-mediated apoptosis.


Asunto(s)
Flavonoles/farmacología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Flavonoles/química , Macrófagos/efectos de los fármacos , Ratones , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología
10.
Int J Mol Sci ; 15(7): 11510-22, 2014 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-24979133

RESUMEN

Expression level of Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.


Asunto(s)
Apigenina/farmacología , Flavonas/farmacología , Flavonoides/farmacología , Macrófagos/efectos de los fármacos , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Animales , Línea Celular , Macrófagos/metabolismo , Ratones , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética
11.
Life (Basel) ; 13(2)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36836951

RESUMEN

TRAIL (Tumor necrosis factor-Related Apoptosis-Inducing Ligand) has the ability to selectively kill cancer cells without being toxic to normal cells. This endogenous ligand plays an important role in surveillance and anti-tumor immunity. However, numerous tumor cells are resistant to TRAIL-induced apoptosis. In this study, the apoptotic effect of santin in combination with TRAIL on colon cancer cells was examined. Flow cytometry was used to detect the apoptosis and expression of death receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5). Mitochondrial membrane potential (ΔΨm) was evaluated by DePsipher staining with the use of fluorescence microscopy. We have shown for the first time that flavonoid santin synergizes with TRAIL to induce apoptosis in colon cancer cells. Santin induced TRAIL-mediated apoptosis through increased expression of death receptors TRAIL-R1 and TRAIL-R2 and augmented disruption of the mitochondrial membrane in SW480 and SW620 cancer cells. The obtained data may indicate the potential role of santin in colon cancer chemoprevention through the enhancement of TRAIL-mediated apoptosis.

12.
Med Sci Monit ; 18(1): BR47-53, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22207109

RESUMEN

BACKGROUND: Photodynamic therapy (PDT) is an attractive, emerging therapeutic procedure suitable for the treatment of non-muscle-invasive bladder cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand that belongs to the TNF superfamily of cytokines. The ability of TRAIL to selectively induce apoptosis in cancer cells but not in normal cells promotes the development of TRAIL-based cancer therapy. However, many tumor cells are resistant to TRAIL-induced apoptosis. The purpose of the study was to overcome TRAIL-resistance in bladder cancer cells by photodynamic therapy (PDT). MATERIAL/METHODS: Three human bladder transitional cancer cell lines - T24, 647V and SW780 - were treated with TRAIL and/or chlorin-based PDT. The cytotoxicity was measured by MTT and LDH assays and apoptosis was detected using annexin V by flow cytometry. RESULTS: Our test confirmed that T24 and 647V bladder cancer cells are resistant to TRAIL, whereas SW780 cells are sensitive to TRAIL. Then we examined the cytotoxic and apoptotic effects of TRAIL in combination with chlorin e6-polyvinylpyrrolidone (Ce6-PVP)-mediated PDT on bladder cancer cells. We showed for the first time that pretreatment with a low dose of PDT significantly sensitizes bladder cancer cells to TRAIL-induced apoptosis. Chlorin-based PDT augments the effect of TRAIL on bladder cancer cells. CONCLUSIONS: PDT with Ce6-PVP photosensitizer enhances the cytotoxic and apoptotic effects of TRAIL on bladder cancer cells. The obtained results suggest that combined treatment by TRAIL and PDT may provide the basis for a new therapeutic approach to induce cell death in bladder cancer.


Asunto(s)
Apoptosis/efectos de los fármacos , Fotoquimioterapia/métodos , Porfirinas/uso terapéutico , Ligando Inductor de Apoptosis Relacionado con TNF/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Análisis de Varianza , Anexina A5 , Línea Celular Tumoral , Citometría de Flujo , Humanos , L-Lactato Deshidrogenasa/metabolismo , Porfirinas/farmacología , Estadísticas no Paramétricas , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Sales de Tetrazolio , Tiazoles
13.
Int J Mol Sci ; 13(11): 15343-59, 2012 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-23203129

RESUMEN

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties.


Asunto(s)
Apoptosis/efectos de los fármacos , Chalcona/farmacología , Neoplasias/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/antagonistas & inhibidores , Línea Celular Tumoral , Chalcona/toxicidad , Sinergismo Farmacológico , Células HeLa , Humanos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/toxicidad
14.
Molecules ; 17(6): 6449-64, 2012 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-22643355

RESUMEN

Coumarins are a very common type of secondary plant metabolites with a broad spectrum of biological activities. Psoralidin is a naturally occurring furanocoumarin isolated from Psoralea corylifolia possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal tissues. Endogenous TRAIL plays an important role in immune surveillance and defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of psoralidin in combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining and mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential. Our study indicated that psoralidin augmented the anticancer effects of TRAIL and confirmed a potential use of coumarins in cancer chemoprevention.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Benzofuranos/farmacología , Cumarinas/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/química , Apoptosis/efectos de los fármacos , Benzofuranos/química , Cumarinas/química , Sinergismo Farmacológico , Expresión Génica/efectos de los fármacos , Células HeLa , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Receptores de Muerte Celular/genética , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/química
15.
Molecules ; 17(10): 11693-711, 2012 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-23027370

RESUMEN

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as the most promising anticancer agent in the TNF superfamily because of its selective cytotoxicity against tumor cells versus normal primary cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated death, it is important to develop new therapeutic strategies to overcome this resistance. Flavonoids have been shown to sensitize cancer cells to TRAIL-induced apoptosis. The aim of this study was to examine the cytotoxic and apoptotic activities of TRAIL on HeLa cancer cells in combination with two synthetic compounds: 6-hydroxyflavanone (6-HF) and its derivative 6-propionoxy-flavanone (6-PF) and to determine the mechanism by which the flavanones overcome the TRAIL-resistance. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected by annexin V-FITC fluorescence staining in flow cytometry and microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression were analysed using flow cytometry. Mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. The synthetic flavanones enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and reduction of mitochondrial membrane potential. Our study indicates that the 6-HF and 6-PF augmented the anticancer effects of TRAIL and confirm a potential use of flavanones in TRAIL-based anticancer therapy and prevention.


Asunto(s)
Antineoplásicos/farmacología , Flavanonas/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Sinergismo Farmacológico , Flavanonas/síntesis química , Flavanonas/toxicidad , Células HeLa , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Receptores de Muerte Celular/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Transducción de Señal/efectos de los fármacos , Ligando Inductor de Apoptosis Relacionado con TNF/toxicidad
16.
Artículo en Inglés | MEDLINE | ID: mdl-19892808

RESUMEN

Prostate cancer is a commonly diagnosed cancer in men. The ethanolic extract of propolis (EEP) and its phenolic compounds possess immunomodulatory, chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone-sensitivity LNCaP and hormone-refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL-induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50 µg mL(-1) EEP and 100 ng mL(-1) TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 cells. The strongest cytotoxic effect on LNCaP cells was exhibited by apigenin, kaempferid, galangin and caffeic acid phenylethyl ester (CAPE) in combination with TRAIL (53.51 ± 0.68-66.06 ± 0.62% death cells). In this work, we showed that EEP markedly augmented TRAIL-mediated apoptosis in prostate cancer cells and suggested the significant role of propolis in chemoprevention of prostate cancer.

17.
Molecules ; 16(5): 3701-12, 2011 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-21540797

RESUMEN

Flavonoids and coumarins are the major bioactive constituents identified in Psoralea corylifolia. The active fraction isolated from fruits, seeds and roots possesses antibacterial, antioxidative and immunomodulatory properties. Neobavaisoflavone is one of the flavonoids found in Psoralea corylifolia. In the present study we investigated in vitro the anti-inflammatory activity of neobavaisoflavone. Macrophages play an important role in inflammation through the release of inflammatory mediators involved in the immune response. Inappropriate and prolonged macrophage activation is largely responsible for the pathology of acute and chronic inflammatory conditions. Neobavaisoflavone significantly inhibited the production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and cytokines: IL-1ß, IL-6, IL-12p40, IL-12p70, TNF-α in LPS+IFN-γ- or PMA- stimulated RAW264.7 macrophages.


Asunto(s)
Antiinflamatorios/farmacología , Mediadores de Inflamación/metabolismo , Isoflavonas/farmacología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Animales , Línea Celular , Ratones
18.
Med Sci Monit ; 16(6): HY11-7, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20512098

RESUMEN

BACKGROUND: The authors hypothesized that the cell redox state might be modified during microbial and viral infections. To detect and evaluate changes in astroglial cell redox state, rat C6 glioma cells after exposure to lipopolysaccharide (LPS) or after herpes simplex virus type 1 (HSV-1) inoculation were used. Redox state modification of glioma cells was determined by the change in menadione-induced superoxide yield. MATERIAL/METHODS: Menadione-induced superoxide formation was registered by the lucigenin-enhanced chemiluminescence (CL) method. RESULTS: The results demonstrate that exposure of C6 glioma cells to LPS for 24 hours resulted in a dose-dependent increase in the mitotic index and integral intensity of menadione-induced lucigenin-enhanced CL. Menadione-induced ROS generation in C6 cells during HSV-1 infection changed depending on the time after HSV-1 inoculation. CONCLUSIONS: The redox state of astroglial cells is modified during microbial and viral infections. The use of redox-active quinones is an informative model for determining cell redox state change and analyzing cells' functional state.


Asunto(s)
Astrocitos/metabolismo , Infecciones Bacterianas/metabolismo , Glioma/metabolismo , Oxidación-Reducción , Virosis/metabolismo , Acridinas/farmacología , Animales , Glioma/microbiología , Glioma/virología , Herpesvirus Humano 1/metabolismo , Cinética , Lipopolisacáridos/metabolismo , Luminiscencia , Mitosis , Ratas , Especies Reactivas de Oxígeno , Vitamina K 3/farmacología
19.
Molecules ; 15(3): 2000-15, 2010 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-20336028

RESUMEN

Isoflavones are a class of bioactive polyphenols with cancer chemopreventive properties. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a naturally occurring antitumor agent that selectively induces programmed death (apoptosis) in cancer cells. Polyphenols can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of isoflavones in combination with TRAIL on HeLa cancer cells. The apoptosis was detected by fluorescence microscopy with annexin V-FITC. The cytotoxicity was evaluated by MTT and LDH assays. The tested isoflavones: genistein, biochanin-A and neobavaisoflavone enhance TRAIL-induced apoptosis in HeLa cells. Our study indicated that isoflavones augmented TRAIL-cytotoxicity against cancer cells and confirmed potential role of those polyphenols in chemoprevention.


Asunto(s)
Apoptosis/fisiología , Isoflavonas/farmacología , Neoplasias/patología , Ligando Inductor de Apoptosis Relacionado con TNF/fisiología , Células HeLa , Humanos
20.
Molecules ; 15(8): 5336-53, 2010 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-20714300

RESUMEN

Chalcones and dihydrochalcones exhibit chemopreventive and antitumor activity. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a natural endogenous anticancer agent. We examined the cytotoxic and apoptotic effect of chalcones and dihydrochalcones on TRAIL-mediated apoptosis in LNCaP prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was detected using annexin V-FITC by flow cytometry and fluorescence microscopy. The DeltaPsim was evaluated using DePsipher staining by fluorescence microscopy. Our study showed that two tested chalcones (chalcone and 2',6'dihydroxy-4'-methoxychalcone) and three dihydrochalcones (2',6'-dihydroxy-4'4-dimethoxydihydrochalcone, 2',6'-dihydroxy-4'-methoxydihydro- chalcone, and 2',4',6'-trihydroxydihydrochalcone, called phloretin) markedly augmented TRAIL-induced apoptosis and cytotoxicity in LNCaP cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.


Asunto(s)
Apoptosis/efectos de los fármacos , Chalconas/farmacología , Neoplasias de la Próstata/patología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Línea Celular Tumoral , Chalconas/química , Sinergismo Farmacológico , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos
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