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Toxicol Appl Pharmacol ; 434: 115822, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896434

RESUMO

Our recent investigation directed to synthesize a novel ruthenium-phloretin complex accompanied by the study of antioxidant in addition to DNA binding capabilities, to determine the chemotherapeutic activity against breast carcinoma in vitro and in vivo. Ruthenium-phloretin complex was synthesized and characterized by different spectroscopic methods. The complex was further investigated to determine its efficacy in both MCF-7 and MDA-MB-231 human carcinoma cell lines and finally in an in vivo model of mammary carcinogenesis induced by DMBA in rats. Our studies confirm that the chelation of the metal and ligand was materialize by the 3-OH and 9-OH functional groups of the ligand and the complex is found crystalline and was capable of intercalating with CT-DNA. The complex was capable of reducing cellular propagation and initiate apoptotic events in MCF-7 and MDA-MB-231 breast carcinoma cell lines. Ruthenium-phloretin complex could modulate p53 intervene apoptosis in the breast carcinoma, initiated by the trail of intrinsic apoptosis facilitated through Bcl2 and Bax and at the same time down regulating the PI3K/Akt/mTOR pathway coupled with MMP9 regulated tumor invasive pathways. Ruthenium-phloretin chemotherapy could interrupt, revoke or suspend the succession of breast carcinoma by altering intrinsic apoptosis along with the anti-angiogenic pathway.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Malus/química , Floretina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Compostos de Rutênio/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Mamárias Animais/induzido quimicamente , Neoplasias Mamárias Animais/tratamento farmacológico , Camundongos , Neoplasias Experimentais , Floretina/química , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Compostos de Rutênio/química , Compostos de Rutênio/toxicidade , Serina-Treonina Quinases TOR , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
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