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1.
Toxicol In Vitro ; 84: 105435, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35817265

RESUMO

In this study, as a new synthesis method, UV light was employed as a type of cross-linking agent to control drug storage and to produce nanoparticles of different sizes and to stabilize the nanoparticles for the first time. We showed that the exposure time of the 5FU albumin solution to UV light produces differences in the size and characterization of the nanoparticles and also produces different cytotoxic effects on MCF-7 breast cancer cells. While the 5FU-A1 nanoparticles we synthesized with 1 h UV storage were approximately 43 nm, the 5FU-A2 nanoparticles we synthesized with UV storage for 3 h increased to an average of 300 nm. 5FU-A1 (IC50 value: 2.5 µg/mL) was approximately 16 times more cytotoxic than free 5FU (IC50 value 39.39 µg/mL) on MCF-7 cancer cells. Moreover, when normal HUVEC cells are treated with 5FU-A1 at a concentration of 2.5 µg/mL, more than 80% of these normal cells remain viable. In addition, we examined the rate of early-to-late apoptosis and necrosis in MCF-7 cancer cells using the Annexin V/PI flow cytometry assay. According to our results, 5FU-A1 promoted the apoptosis pathway. Finally, we examined P-gp activity with MDR1/ABCB1 antibody by flow cytometry and Rhodamine123 with fluorescent dye.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Albuminas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Neoplasias da Mama/tratamento farmacológico , Feminino , Fluoruracila/farmacologia , Humanos , Células MCF-7 , Raios Ultravioleta
2.
Chem Biol Interact ; 363: 109997, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35654126

RESUMO

In order to examine the anticancer potential of oxovanadium(IV) complexes with thiosemicarbazone, two new complexes were prepared starting from 2-thenoyltrifluoroacetone-S-methylthiosemicarbazone. The complexes with tetradentate thiosemicarbazone ligand were characterized by elemental analysis, IR, ESI MS, and single-crystal X-ray diffraction analysis. Cytotoxicity on breast cancer cells, MDA-MB-231 and MCF-7, was determined by MTT assay. Cisplatin was positive control and the results were compared with those of the normal cells, HUVEC and 3T3. The complexes exhibited greater activity on cancer cells than cisplatin, but they were cytotoxic at several times higher concentrations in the healthy cells. In our study, the presence of thiophene and fluoro groups in the oxovanadium(IV) complexes with thiosemicarbazone increased greatly the cytotoxic activity of the complexes on breast cancer cells. Moreover, the complexes induced apoptosis-mediated cell death and also reduced the expression of MDR-1 or P-glycoprotein and ABCG2. As a result, the findings indicated that the complexes have selective cytotoxicity on breast cancer cells and can overcome multidrug resistance. These properties of the complexes make it possible to be a potential anticancer drug candidate for breast cancer treatment.


Assuntos
Antineoplásicos , Neoplasias da Mama , Complexos de Coordenação , Tiossemicarbazonas , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Resistência a Medicamentos , Feminino , Humanos , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia
3.
Sci Rep ; 12(1): 10686, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35739313

RESUMO

Carboplatin (CP), a platinum analog, is one of the most widely used chemotherapeutic agents in the treatment of colorectal cancer. Although platinum-based drugs are quite effective in anticancer treatments, their use in a wide spectrum and effective treatment possibilities are limited due to their systemic side effects and drug resistance development. In recent years, studies have focused on increasing the therapeutic efficacy of platinum-based drugs with drug delivery systems. Gelatin, a protein, obtained by the hydrolysis of collagen, is a biocompatible and biodegradable material that can be used in nano drug delivery systems. In this study, CP-loaded gelatin-based NPs (CP-NPs) were exposed to IR light in different temperatures at 30, 35, 40, 45, and 50 °C and characterized by FESEM-EDX, FTIR, UV-Vis, DLS. Accordingly, we synthesized gelatin-based CP-NPs of different sizes between 10-290 nm by exposure to IR. We found that CP-NPs-50, 16 nm nano-sized, obtained at 50 °C had the most cytotoxicity and was 2.2 times more effective than the free drug in HCT 116 colon cancer cells. Moreover, we showed that the cytotoxicity of CP-NPs-50 in normal HUVEC cells was lower. Additionally, we demonstrated that CP-NPs enhanced apoptotic activity while not developing MDR1-related resistance in colon cancer cells. In this study, for the first time drug loaded gelatin-based nanoparticles were synthesized in different sizes with a newly self-assembly method by exposing them to infrared light at different temperatures and their anticancer effects were evaluated subsequently.


Assuntos
Antineoplásicos , Neoplasias do Colo , Nanopartículas , Antineoplásicos/farmacologia , Carboplatina/farmacologia , Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Gelatina , Humanos
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