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1.
Lasers Med Sci ; 38(1): 70, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36780027

RESUMEN

Canine mammary sarcoma tumors (CMST) are the most aggressive tumors with poor prognosis in dogs. Due to inadequate treatment options for CMST, recent studies have focused on alternative treatment strategies. We previously determined the optimized protocol of 5-ALA-based photodynamic therapy (PDT) in canine liposarcoma. However, its molecular mechanisms in the treatment of different histological types of CMST remain unclear.In this context, we, for the first time, assessed 5-aminolevulinic acid (5-ALA)-PDT-mediated anti-cancer activity and its molecular mechanism after continuous wave (CW) and pulse radiation (PR) on three different histological types (liposarcoma, chondrosarcoma, and osteosarcoma) of CMST cells by WST-1, Annexin V, ROS, acridine orange/propidium iodide staining, RT-PCR, and western blot analysis.Our findings showed that 5-ALA/PDT significantly suppressed the proliferation of CMST cells (p < 0.01) and induced apoptosis via increased ROS level and overexpression of Caspase-9 and Caspase-3 mRNA and cleaved protein levels in especially liposarcoma and chondrosarcoma cells following CW and PR irradiation at 9 J/cm2. However, the response of CMST cells to 5-ALA was different upon CW and PR irradiation due to differences in their origin.Collectively, our findings provided the first evidence that 5-ALA-based PDT could be used as an alternative treatment strategy, especially liposarcoma and chondrosarcoma. However, further in vitro and in vivo studies are required to elucidate the underlying molecular mechanism of the efficacy of 5-ALA in CMST cells at the molecular level.


Asunto(s)
Condrosarcoma , Liposarcoma , Fotoquimioterapia , Sarcoma , Perros , Animales , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Fotoquimioterapia/métodos , Línea Celular Tumoral , Apoptosis/efectos de la radiación , Liposarcoma/tratamiento farmacológico , Liposarcoma/genética , Liposarcoma/radioterapia , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico
2.
Lasers Med Sci ; 37(2): 867-876, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33937952

RESUMEN

Canine mammary gland tumors (CMGTs) are heterogeneous disease and subclassified [sarcomas (S), carcinomas (C), and carcinosarcomas (CS)] according to histopathological differentiation. Photodynamic therapy (PDT) is a promising treatment strategy based on the use of a photosensitizer (PS) activated by light. However, the therapeutic potential of PDT in the treatment of CMGTs has not been investigated, yet. Therefore, the aim of this study was to determine the in vitro protocol of 5-ALA-based-PDT for the treatment of three subtypes of CMGTs, for the first time. The intracellular PpIX florescence intensity was measured for 5-ALA (0.5 and 1 mM). After irradiation with different light doses (6, 9, 12, 18, and 24 J/cm2) for two different modes [continuous wave (CW) and pulse radiation (PR)], the cytotoxic effects of 5-ALA (0.5 and 1 mM) on the subtypes (C, S, and CS) of CMGTs were analyzed by WST-1. Finally, the optimal PDT treatment protocol was validated through Annexin V and AO/EtBr staining. Our results showed that 1 mM 5-ALA for 4-h incubation was the best treatment condition in all subtypes of CMGTs due to higher intracellular PpIX level. After irradiation with different light doses, PR mode was more effective in S primary cells at 9 J/cm2. However, a significant decrease in the viability of C and CS cells was detected at 12 /cm2 in CW mode (p < 0.05). Additionally, 1 mM 5-ALA induced apoptotic cell death in each subtype of CMGTs. Our preliminary findings suggest that (i) each subtype of CMGTs differentially responds to PDT and (ii) the light dose and mode could play an important role in the effective PDT treatment. However, further studies are needed to investigate the role of the different light sources and PDT-based apoptotic cell death in CMGTs cells.


Asunto(s)
Neoplasias , Fotoquimioterapia , Ácido Aminolevulínico/farmacología , Animales , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Perros , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Protoporfirinas/farmacología
3.
Drug Chem Toxicol ; 40(3): 300-308, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27631679

RESUMEN

In this study, a Cd(II) complex was synthesized using 8-hydroxyquinoline and thiocyanate as the ligands and structurally characterized with the combination of FTIR, 1H-NMR, 13C-NMR, UV-vis, and MS spectral data. Then, genotoxic effects of the prepared complex were investigated. Genotoxic properties of the dimeric 8-hydroxyquinolinthiocyanatoCd(II) [Cd2(8Q)2(SCN)2] complex synthesized as drug raw material were analyzed in human peripheral blood lymphocytes. Concentrations of 1, 2, 4, 6, and 8 µg/mL [Cd2(8Q)2(SCN)2] were used for 24 and 48 h durations. [Cd2(8Q)2(SCN)2] significantly increased chromosomal aberrations (CAs) at 4, 6, and 8 µg/mL concentrations after a 24- h period and 2 and 4 µg/mL after a 48-h period. [Cd2(8Q)2(SCN)2] significantly decreased the mitotic index (MI) at all concentrations, both at 24 and 48 h. Micronuclei frequency (MN) was not affected by [Cd2(8Q)2(SCN)2] treatment compared with the control. After application for a 48 h period, 6 and 8 µg/mL concentrations showed toxic effects both in chromosomal abnormality and in micronucleus tests. It also decreased the cytokinesis-block proliferation index (CBPI), but this result was statistically significant only at 6 and 8 µg/mL concentrations. In the comet assay (single-cell gel electrophoresis (SCGE)), significant increases in comet tail length, tail moment, and tail intensity were observed at all concentrations. [Cd2(8Q)2(SCN)2] displays clastogenic effect in the concentrations used in human peripheral lymphocytes at chromosomal abnormality, micronucleus tests, and cytokinesis-block proliferation index parameters. Further studies should be conducted in other test systems to evaluate the complete genotoxic potential of [Cd2(8Q)2(SCN)2].


Asunto(s)
Aberraciones Cromosómicas/inducido químicamente , Complejos de Coordinación , Daño del ADN , Linfocitos/efectos de los fármacos , Mutágenos , Células Cultivadas , Aberraciones Cromosómicas/estadística & datos numéricos , Ensayo Cometa , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Complejos de Coordinación/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Linfocitos/patología , Masculino , Micronúcleos con Defecto Cromosómico/inducido químicamente , Micronúcleos con Defecto Cromosómico/estadística & datos numéricos , Pruebas de Micronúcleos , Índice Mitótico , Mutágenos/síntesis química , Mutágenos/química , Mutágenos/toxicidad
4.
Cureus ; 14(10): e29989, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36381770

RESUMEN

Background Chlorine dioxide (ClO2) is an effective disinfectant consisting of oxygen, chloride, and potassium. Because of its high oxidative capacity, ClO2 exerts antimicrobial, antiviral, and antifungal effects. However, its anticancer effects remain to be elucidated. Methodology The anticancer activity of CIO2 was assessed on DMS114 small-cell lung cancer (SCLC) cells and human umbilical vein endothelial cells (HUVEC) as control by WST-1, Annexin V, cell cycle analysis, and acridine orange staining. We for the first time investigated the possible therapeutic effects of long-term stabilized ClO2 solution (LTSCD). Results Our preliminary findings showed that LTSCD significantly inhibited the proliferation of SCLC cells (p < 0.01) with less toxicity in HUVEC cells. Additionally, LTSCD induced apoptotic cell death in SCLC cells through nuclear blebbing and vacuolar formation. However, LTSCD treatment did not induce cell cycle arrest in both cell lines. Conclusions LTSCD can be a therapeutic potential for the treatment of SCLC. However, further investigations are required to assess the LTSCD-induced cell death in SCLC both in vitro and in vivo.

5.
Acta Crystallogr E Crystallogr Commun ; 75(Pt 6): 780-784, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-31391965

RESUMEN

This work presents the synthesis and structural characterization of [4-(1H-benzo[d]imidazol-2-yl)phen-oxy]phthalo-nitrile, a phthalo-nitrile derivative carrying a benzimidazole moiety. The compound crystallizes as its dimethyl sulfoxide monosolvate, C21H12N4O·(CH3)2SO. The dihedral angle between the two fused rings in the heterocyclic ring system is 2.11 (1)°, while the phenyl ring attached to the imidazole moiety is inclined by 20.7 (1)° to the latter. In the crystal structure, adjacent mol-ecules are connected by pairs of weak inter-molecular C-H⋯N hydrogen bonds into inversion dimers. N-H⋯O and C-H⋯O hydrogen bonds with R 2 1(7) graph-set motifs are also formed between the organic mol-ecule and the disordered dimethyl sulfoxide solvent [occupancy ratio of 0.623 (5):0.377 (5) for the two sites of the sulfur atom]. Hirshfeld surface analysis and fingerprint plots were used to investigate the inter-molecular inter-actions in the crystalline state.

6.
Dalton Trans ; 45(25): 10402-10, 2016 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-27253970

RESUMEN

In this study, 4-{4-[N-((3-dimethylamino)propyl)amide]phenoxy}phthalonitrile () and its zinc(ii) phthalocyanine derivative () were synthesized for the first time. 4-(N-((3-Dimethylamino)propyl)amide)phenoxy substituted zinc(ii) phthalocyanine () was converted to its water-soluble sulfobetaine (), betaine () and N-oxide () containing zwitterionic and quaternized cationic () derivatives. All newly synthesized compounds () were characterized by the combination of UV-vis, FT-IR, (1)H NMR, mass spectroscopy techniques and elemental analysis. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen quantum yields) properties were investigated in DMSO for all the synthesized zinc(ii) phthalocyanines () and in both DMSO and aqueous solutions for zwitterionic and cationic phthalocyanines () for the specification of their capability as photosensitizers in photodynamic therapy (PDT). The binding behavior of water soluble phthalocyanines () to the bovine serum albumin protein was also examined for the determination of their transportation ability in the blood stream.


Asunto(s)
Indoles/metabolismo , Compuestos Organometálicos/metabolismo , Fármacos Fotosensibilizantes/metabolismo , Animales , Derivados del Benceno/química , Betaína/química , Bovinos , Indoles/química , Isoindoles , Compuestos Organometálicos/química , Procesos Fotoquímicos , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Compuestos de Amonio Cuaternario/química , Albúmina Sérica Bovina/química , Oxígeno Singlete/metabolismo , Solubilidad , Espectrometría de Fluorescencia , Agua/química , Compuestos de Zinc
7.
Acta Crystallogr E Crystallogr Commun ; 71(Pt 9): 1042-4, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26396843

RESUMEN

In the title compound, C20H20N4O2·H2O, the planes of the phen-oxy and phthalo-nitrile rings are oriented at a dihedral angle of 60.39 (5)°. The 3-(di--methyl-amino)-propyl chain has an extended conformation and is cis with respect to the phthalo-nitrile ring. In the crystal, O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds link the mol-ecules to form slabs parallel to (100). There are also C-H⋯O and C-H⋯N hydrogen bonds and C-H⋯π inter-actions present within the slabs. The slabs are linked by a pair of inversion-related C-H⋯N hydrogen bonds, involving phthalo-nitrile rings, forming a three-dimensional structure.

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