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J Inorg Biochem ; 230: 111720, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35221123

RESUMO

In vivo toxicity of aromatic ring (BODIPY, 1,3,5,7,8-pentamethyl dipyrrin borondifluoride) attached monofunctional Pt(II) complexes mCBP {[cis-Pt(NH3)2Cl] 8-(para-pyridine-methylene),1,3,5,7-tetramethyl dipyrrin borondifluoride}+ Nitrate- and dCBP {[cis-Pt(NH3)2Cl]28-(1,3-pyrimidine-5-methylene),1,3,5,7-tetramethyl dipyrrin borondifluoride}2+ diNitrate2- were tested in Caenorhabditis elegans (C. elegans). dCBP showed promising reactive oxygen ROS (reactive oxygen species) generating capability. This complex resulted reduction of lifespan, body length and egg laying rate under dark and light irradiation in both N2 (wild-type, cisplatin resistant) and ok938 (asna-1, cisplatin sensitive) C. elegans. Expressional change of several key cancer related pathway (JNK (c-Jun N-terminal kinase) and Wnt/ß-catenin (Wingless/Integrated/ß-catenin)) related genes (for instance, jnk-1, wrm-1 and gst-4) were confirmed by RNA sequencing experiments. These transcriptional alternations could explain physiological parameters change in nematode and partially revealed how both Pt(II) based complexes influence cancer related pathways. Furthermore, these associated genes exhibited the function of apoptosis, reduced chemoresistance of cancer cells and most of those expressional changes were linked to extended survival of cancer patients.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Platina/farmacologia , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Cisplatino/farmacologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/farmacologia , Humanos , Espécies Reativas de Oxigênio/metabolismo , beta Catenina/metabolismo , beta Catenina/farmacologia
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