Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
1.
Bioorg Chem ; 104: 104276, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32992280

RESUMO

Novel lead compounds as anticancer agents with the ability to circumvent emerging drug resistance have recently gained a great deal of interest. Thiazolidinones are among such compounds with well-established biological activity in the field of oncology. Here, we designed, synthesized and characterized a series of thiazolidinone structures (8a-8k). The results of anti-proliferative assay led to the discovery of compound 8j with a high potent cytotoxic effect using colon, liver and breast cancer cells. Furthermore, MDA-MB-231 and 4T1 cell lines were used to represent triple negative breast cancer (TNBC). Next, a number of in vitro and in vivo evaluations were carried out to demonstrate the potential activity against TNBC and also elucidate the possible mechanism of cell death induction. Our in vitro outcomes exhibited an impressive anticancer activity for compound 8j toward MDA-MB-231 cells through inducing apoptosis and a remarkable anti-metastatic feature via suppressing MMP-9 expression as well. Consistently, the in vivo and immunohistopathologic evaluations demonstrated that this compound significantly inhibited the 4T1 induced tumor growth and its metastasis to the lung. Altogether, among numerous thiazolidinone derivatives, compound 8j might represent a promising anticancer agent for TNBC, which is a major concern in the developed and developing countries.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Desenho de Fármacos , Tiazolidinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Relação Estrutura-Atividade , Tiazolidinas/síntese química , Tiazolidinas/química , Células Tumorais Cultivadas
2.
Biol Res ; 52(1): 40, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387647

RESUMO

BACKGROUND: There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics. METHODS: 4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5-7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells. RESULTS: Our results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control. CONCLUSION: This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Metástase Neoplásica/prevenção & controle , Animais , Linhagem Celular Tumoral , Feminino , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C
3.
BMC Complement Altern Med ; 19(1): 116, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164129

RESUMO

BACKGROUND: Allium species are magnificently nutritious and are commonly used as a part of the diet in Iran. They have health enhancing benefits including anticancer properties due to the presence of numerous bioactive compounds. Herein, we investigated in vitro and in vivo anticancer properties of Allium bakhtiaricum extracts. METHODS: Anti-growth activity of different fractions was explored in vitro on different cancerous cells using MTT assay, Annexin V/PI and SA-ß-gal staining, Western blotting, flowcytometric and immunofluorescence microscopic evaluations. In vivo antitumor activity was investigated in BALB/c mice bearing 4 T1 mammary carcinoma cells. RESULTS: We demonstrated that chloroformic and ethyl acetate fractions exert cytotoxic activity toward MDA-MB-231 cells, the most sensitive cell line, after 72 h of treatment with IC50 values of 0.005 and 0.006 mg/ml, respectively. Incubation of MDA-MB-231 cells with » and ½ IC50-72h concentrations of each fraction resulted in a significant G2/M cell cycle arrest. » IC50-72h concentration of the chloroform fraction led to the disruption of polymerization in mitotic microtubules. Exposure of human breast cancer cells to different concentrations of the extracts at different incubation times did not induce apoptosis, autophagy or senescence. Our in vivo study revealed that administration of the chloroform extract at a dose of 1 mg/kg/day strongly suppressed mammary tumor progression and decreased the number of proliferative cells in the lung tissues indicating its anti-metastatic effect. CONCLUSION: Our findings imply that the chloroform fraction of Allium bakhtiaricum possesses the suppressive action on breast cancer through mitotic cell cycle arrest suggesting a mechanism associated with disturbing microtubule polymerization.


Assuntos
Allium/química , Antineoplásicos Fitogênicos/análise , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microtúbulos/efeitos dos fármacos , Metástase Neoplásica , Extratos Vegetais/química , Extratos Vegetais/farmacologia
4.
Naunyn Schmiedebergs Arch Pharmacol ; 397(7): 5119-5129, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38240779

RESUMO

Triple-negative breast cancer is a subtype of breast cancer with poor clinical outcome, and currently, no effective targeted therapies are available. Since cancer develops owing to deregulation of apoptosis, employing therapeutic strategies with the ability to target the molecules involved in apoptosis induction would provide a valid approach to hinder tumor progression. Hydrazide-hydrazones and oxamide molecules are the subject of intense studies due to their anticancer effects via apoptosis induction. In the present study, we attempted to elucidate the mechanism of action of a synthesized compound (compound A) in inducing cell death. Annexin/PI and Western blotting analyses, DAPI staining, mitochondrial membrane potential probe, and flow cytometry were applied for the in vitro evaluations. 4T1 syngeneic mouse model and immunohistochemistry were used for the in vivo assessments. Compound A caused cell death by inducing apoptosis in MDA-MB-231 cells in a mitochondrial-dependent manner at high concentrations after 72 h of incubation. Compound A also impeded tumor growth in a 4T1 syngeneic mouse model as evidenced by hematoxylin and eosin staining of the tumors. Furthermore, it significantly diminished the expression of pro-caspase-3, Ki67, and CD31 markers in the tumor sections. Conclusively, this study for the first time reports the anti-cancer efficacy of compound A in both in vitro and in vivo models and its potential in the treatment of triple-negative breast cancer.


Assuntos
Antineoplásicos , Apoptose , Hidrazonas , Camundongos Endogâmicos BALB C , Neoplasias de Mama Triplo Negativas , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Hidrazonas/farmacologia , Hidrazonas/síntese química , Hidrazonas/uso terapêutico , Feminino , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Humanos , Camundongos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Antígeno Ki-67/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo
5.
Iran J Pharm Res ; 19(2): 145-152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224219

RESUMO

Prognosis of metastatic breast cancer is very poor which urges the necessity to develop novel potential drug candidates. We assessed two compounds with tri-aryl structures (A and B) for their potency to reduce primary breast tumor growth and lung metastasis in 4T1 mice model. MTT assay, 4T1 mammary mouse model, and immunohistochemistry experiments were used in this study. In-vitro results exhibited an anti-proliferative effect for compounds A and B towards MDA-MB-231 cancer cells. Our in-vivo results displayed that administered compounds A and B could suppress the size of the primary tumor and the number of lung metastatic foci in 4T1 BALB/c mice model. Histopathological analysis revealed that treatment of both compounds resulted in necrosis. Our findings provide new evidence that compound B may be promising for slowing the growth of tumor along with metastatic foci via COX-2 independent pathway.

6.
Cancer Chemother Pharmacol ; 79(6): 1195-1203, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28451832

RESUMO

PURPOSE: The hydrazide backbone is a well-known structural core system found in a broad range of biologically activated compounds. Among which, the compounds with anticancer activity have been cited in a number of studies. With this object in mind, we focused on the in vitro and in vivo anticancer potential of two novel hydrazide derivatives bearing furan or thiophen substituents (compounds 1 and 2). METHODS: The cytotoxic property was evaluated using MTT assay against MCF-7 human breast adenocarcinoma cell line, while the in vivo antitumor activity was investigated in BALB/c mice bearing 4T1 mammary carcinoma cells. Flow cytometry was used for cell cycle analysis, and detection of apoptosis was examined by Annexin-V-FLUOS/PI assay. Protein expression of Bax, Bcl-2 and procaspase-3 was estimated by Western blotting. RESULTS: Compounds 1 and 2 were found to be cytotoxic towards breast cancer cells presenting IC50 values of 0.7 and 0.18 µM, respectively, and selectivity over normal fibroblast cells. Our findings further indicated that 2 × IC50 concentrations of both compounds induce early stage apoptosis and increase percentage of sub-G1 population in MCF-7 cells at 48 h. An elevation in Bax/Bcl-2 ratio and caspase-3 cleavage suggested that apoptosis induced by the two compounds is through a caspase- and mitochondrial-dependent pathway. In the in vivo study, compounds 1 and 2 at doses of 10 and 1 mg/Kg/day, respectively, significantly hindered the growth of tumor after 3 weeks of i.p. administration, when compared to vehicle-treated mice. CONCLUSION: Collectively, the great potential exhibited by compound 2 could make it a promising chemotherapeutic candidate for human cancers, especially for breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Hidrazinas/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Caspase 3/biossíntese , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Furanos , Fase G1/efeitos dos fármacos , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Tiofenos , Proteína X Associada a bcl-2/biossíntese
7.
Biol. Res ; 52: 40, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1019504

RESUMO

BACKGROUND: There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics. METHODS: 4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5-7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells. RESULTS: Our results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control. CONCLUSION: This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer.


Assuntos
Animais , Feminino , Camundongos , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Metástase Neoplásica/prevenção & controle , Antineoplásicos/farmacologia , Imuno-Histoquímica , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA