RESUMEN
The phenotype of multidrug resistance (MDR) is one of the main causes of chemotherapy failure. Our study investigated the effect of C-phycocyanin (C-PC) in three human erythroleukemia cell lines with or without the MDR phenotype: K562 (non-MDR; no overexpression of drug efflux proteins), K562-Lucena (MDR; overexpression of ATP-binding cassette, sub-family B/ABCB1), and FEPS (MDR; overexpression of ABCB1 and ATP-binding cassette, sub-family C/ABCC1). Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed that 20 and 200⯵g/mL C-PC decreased K562 viable cells after 24â¯h and 200⯵g/mL C-PC decreased K562-Lucena cell proliferation after 48â¯h. C-PC did not decrease viable cells of FEPS cells. On the other hand, the MTT assay showed that exposure of 2, 20, and 200⯵g/mL C-PC for 24 or 48â¯h was not cytotoxic to peritoneal macrophages. At 72â¯h, the trypan blue exclusion assay showed that 20⯵g/mL C-PC decreased K562 and K562-Lucena cell proliferation and in FEPS cells, only 200⯵g/mL C-PC decreased proliferation. In addition, protein-protein docking showed differences in energy and binding sites of ABCB1 and ABCC1 for C-PC, and these results were confirmed by the efflux protein activity assay. Only ABCC1 activity was altered in the presence of C-PC and FEPS cells showed lower C-PC accumulation, suggesting C-PC extrusion by ABCC1, conferring C-PC resistance. In combination with chemotherapy (vincristine [VCR] and daunorubicin [DNR]), the sensitivity of K562-Lucena cells for C-PCâ¯+â¯VCR did not increase, whereas FEPS cell sensitivity for C-PCâ¯+â¯DNR was increased. In molecular docking experiments, the estimated free energies of binding for C-PC associated with chemotherapy were similar (VCR: -6.9â¯kcal/mol and DNR: -7.2â¯kcal/mol) and these drugs were located within the C-PC cavity. However, C-PC exhibited specificity for tumor cells and K562 cells were more sensitive than K562-Lucena cells, followed by FEPS cells. Thus, C-PC is a possible chemotherapeutic agent for cells with the MDR phenotype, both alone in K562-Lucena cells (resistance due to ABCB1), or in combination with other drugs for cells similar to FEPS (resistance due to ABCC1). Moreover, C-PC did not damage healthy cells (peritoneal macrophages of Mus musculus).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Daunorrubicina/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Ficocianina/farmacología , Vincristina/farmacología , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Sitios de Unión , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células K562 , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/metabolismo , Leucemia Eritroblástica Aguda/patología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/patología , Ratones , Simulación del Acoplamiento Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Ficocianina/metabolismo , Ficocianina/toxicidad , Unión Proteica , Conformación Proteica , Factores de TiempoRESUMEN
Reoccurring seasonal cyanobacterial harmful algal blooms (CHABs) persist in many waters, and recent work has shown links between CHAB and elevated risk of amyotrophic lateral sclerosis (ALS). Quantifying the exposure levels of CHAB as a potential risk factor for ALS is complicated by human mobility, potential pathways, and data availability. In this work, we develop phycocyanin concentration (i.e., CHAB exposure) maps using satellite remote sensing across northern New England to assess relationships with ALS cases using a spatial epidemiological approach. Strategic semi-analytical regression models integrated Landsat and in situ observations to map phycocyanin concentration (PC) for all lakes greater than 8 ha (n = 4117) across the region. Then, systematic versions of a Bayesian Poisson Log-linear model were fit to assess the mapped PC as a risk factor for ALS while accounting for model uncertainty and modifiable area unit problems. The satellite remote sensing of PC had strong overall ability to map conditions (adj. R2, 0.86; RMSE, 11.92) and spatial variability across the region. PC tended to be positively associated with ALS risk with the level of significance depending on fixed model components. Meta-analysis shows that when average PC exposure is 100 µg/L, an all model average odds ratio is 1.48, meaning there is about a 48% increase in average ALS risk. This research generated the first regionally comprehensive map of PC for thousands of lakes and integrated robust spatial uncertainty. The outcomes support the hypothesis that cyanotoxins increase the risk of ALS, which helps our understanding of the etiology of ALS.
Asunto(s)
Esclerosis Amiotrófica Lateral/etiología , Cianobacterias/química , Floraciones de Algas Nocivas , Ficocianina/toxicidad , Esclerosis Amiotrófica Lateral/epidemiología , Animales , Ecosistema , Monitoreo del Ambiente , Humanos , Lagos , Modelos Estadísticos , New England/epidemiología , Ficocianina/química , Estudios Retrospectivos , Factores de Riesgo , Comunicaciones por SatéliteRESUMEN
Photodynamic therapy (PDT), combining the laser and photosensitizers to kill tumor cells, has the potential to address many current medical requirements. In this study, magnetic Fe3O4 nanoparticles were first employed as cores and modified with oleic acid (OA) and 3-triethoxysilyl-1-propanamine. Then, the photosensitizers phycocyanin (PC) and hematoporphyrin monomethyl ether (HMME), which might be able to stimulate the cell release of reactive oxygen species after the irradiation of a near-infrared (NIR) laser, were grafted on the surface of such nanoparticles. Our results revealed the high-efficiency inhibition of breast cancer MCF-7 cells growing upon near-infrared irradiation both in vitro and in vivo. Furthermore, it was the synergy between the natural photosensitizers PC and the synthetic photosensitizers HMME that deeply influenced such inhibition compared to the groups that used either of these medicines alone. To utilize the combination of different photosensitive agents, our study thus provides a new strategy for breast cancer treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Hematoporfirinas/uso terapéutico , Nanopartículas de Magnetita/química , Fármacos Fotosensibilizantes/química , Ficocianina/uso terapéutico , Animales , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Femenino , Hematoporfirinas/administración & dosificación , Hematoporfirinas/farmacología , Hematoporfirinas/toxicidad , Humanos , Rayos Infrarrojos , Células MCF-7 , Nanopartículas de Magnetita/toxicidad , Ratones Endogámicos BALB C , Fotoquimioterapia , Ficocianina/administración & dosificación , Ficocianina/farmacología , Ficocianina/toxicidadRESUMEN
In this study the culture filtrate and C-phycocyanin obtained from filamentous fresh water cyanobacterium Westiellopsis sps were tested for their antibacterial activity against three different bacterial cultures: Bacillus subtilis, Pseudomonas sps and Xanthomonas sps. The growth of all bacterial strains tested was inhibited by the culture filtrate and C-phycocyanin. The diameter of inhibition zones varied from 1.3 to 13.2 mm and from 2.2 to 13.1 mm for the culture filtrate and C-phycocyanin, respectively. It is therefore suggested that extracts from the Westiellopsis sps could be used traditionally in the treatment of bacterial infections. Bioassay studies of silkworm showed that there was no symptom of ill health after feeding the phycocyanin treated leaves and the body weight and silk gland weight of the silkworm increased with range of 65.0-102.6 mg and 209-240 mg respectively compared to the control.
Asunto(s)
Antibacterianos/farmacología , Cianobacterias/química , Ficocianina/farmacología , Animales , Antibacterianos/aislamiento & purificación , Bacillus subtilis/efectos de los fármacos , Bombyx , Extractos Celulares/aislamiento & purificación , Extractos Celulares/farmacología , Pruebas de Sensibilidad Microbiana , Ficocianina/aislamiento & purificación , Ficocianina/toxicidad , Pseudomonas/efectos de los fármacos , Pruebas de Toxicidad , Xanthomonas/efectos de los fármacosRESUMEN
OBJECTIVE: To examine the effects of C-phycocyanin, a pigment found in blue-green algae which acts as an antioxidant in vitro and in vivo, in different animal models of inflammation. MATERIAL: Male Sprague Dawley rats and OF1 mice were used. TREATMENTS: Oedema was induced by: a) AA (0.5 mg/ear) or TPA (4 microg/ear) in the mouse ear b) carrageenan injection (0.1 mL of 1% suspension) in the rat paw (+/-adrenalectomy) and c) cotton pellet implantation in the rat axilla. Phycocyanin (50-300mg/kg, p.o.) or indomethacin (1 mg/ear or 3-10mg/kg, p.o.) as control were tested in the four animal models. METHODS: Measurement of the increase in the weight (mg) of 6 mm ear punch biopsies from treated ears were made in comparison to control ears, together with myeloperoxidase (MPO) activity as an index of neutrophil infiltration. The increase in the paw thickness (mm) was measured with a dial caliper. Cotton pellet was implanted and seven days afterwards the granuloma was removed and the dry weight was determined. Acute toxicity was studied in mice and rats. Statistics were performed using one-way analysis of variance with the Duncan Multirange test. RESULTS: Phycocyanin reduced significantly (p < 0.05) and in a dose-dependent manner ear oedema induced by AA and TPA in mice as well as carrageenan-induced rat paw oedema (both in intact and adrenalectomized animals). In the TPA test, phycocyanin also reduced MPO content. Phycocyanin also exerted an inhibitory effect in the cotton pellet granuloma test. In the acute toxicity test in rats and mice, even at the highest dose tested (3000 mg/kg, p.o.), no toxicity was found. CONCLUSIONS: Phycocyanin shows anti-inflammatory activity in four experimental models of inflammation. Its antioxidative and oxygen free radical scavenging properties may contribute, at least in part, to its anti-inflammatory activity.