Carnizello Andréa P, Barbosa Marília I F, Martins Monize, Ferreira Natália H, Oliveira Pollyanna F, Magalhães Geórgia M, Batista Alzir A, Tavares Denise C
Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil; Laboratório de Mutagênese, Universidade de Franca, Pq. Universitario, CEP14404-600 Franca, SP, Brazil.
Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil.
J Inorg Biochem. 2016 Nov;164:42-48. doi: 10.1016/j.jinorgbio.2016.08.010. Epub 2016 Aug 25.
This study performed in vitro and in vivo biological assays of the ruthenium (II) compound ct-[RuCl(CO)(dppb)(bipy)]PF (where, dppb=1,4-bis(diphenylphosphine)butane and bipy=2,2'-bipyridine). The cytotoxic activity of this compound was evaluated against different tumor cell lines (HeLa, human cervical adenocarcinoma; MCF7, human breast adenocarcinoma; MO59J, human glioblastoma; HepG2, hepatocellular carcinoma and B16F10, murine melanoma) and healthy cell line (V79, Chinese hamster lung fibroblasts), by XTT (sodium 2,3'-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-3,4-tetrazolium-bis(4-methoxy-6-nitro)benzene-sulfonic acid hydrate) method. A syngeneic murine melanoma tumor model (B16F10) was used to evaluate its antitumor activity. Additionally, experiments were performed to assess the interactions with ctDNA (calf thymus DNA) and BSA (bovine serum albumin). The results showed that ct-[RuCl(CO)(dppb)(bipy)]PF was cytotoxic against all tumor cell lines tested. Furthermore, the compound was more effective against tumor cells compared to the normal cell line, indicating selectivity, especially in B16F10 cells. Significant tumor growth reduction was observed in animals treated with the compound compared to the untreated control. Histopathological analysis of tumor tissue revealed a significant reduction of mitosis in animals treated with the compound compared to the untreated control. In the ctDNA and BSA interaction experiments, the compound in study showed weak interactions with ctDNA and hydrophobic interactions with BSA. The ruthenium compound investigated showed promising results in in vitro and in vivo biological assays.
本研究对钌（II）化合物ct-[RuCl(CO)(dppb)(bipy)]PF（其中，dppb = 1,4 - 双（二苯基膦）丁烷，bipy = 2,2'-联吡啶）进行了体外和体内生物学测定。通过XTT（2,3'-双（2 - 甲氧基 - 4 - 硝基 - 5 - 磺基苯基）-5 - [（苯基氨基）羰基] - 3,4 - 四唑鎓 - 双（4 - 甲氧基 - 6 - 硝基）苯磺酸水合物）法评估了该化合物对不同肿瘤细胞系（HeLa，人宫颈腺癌；MCF7，人乳腺腺癌；MO59J，人胶质母细胞瘤；HepG2，肝细胞癌；B16F10，小鼠黑色素瘤）和健康细胞系（V79，中国仓鼠肺成纤维细胞）的细胞毒性活性。使用同基因小鼠黑色素瘤肿瘤模型（B16F10）评估其抗肿瘤活性。此外，还进行了实验以评估与ctDNA（小牛胸腺DNA）和BSA（牛血清白蛋白）的相互作用。结果表明，ct-[RuCl(CO)(dppb)(bipy)]PF对所有测试的肿瘤细胞系均具有细胞毒性。此外，与正常细胞系相比，该化合物对肿瘤细胞更有效，表明具有选择性，尤其是在B16F10细胞中。与未处理的对照组相比，在用该化合物处理的动物中观察到肿瘤生长明显减少。肿瘤组织的组织病理学分析显示，与未处理的对照组相比，用该化合物处理的动物中细胞有丝分裂明显减少。在ctDNA和BSA相互作用实验中，所研究的化合物与ctDNA表现出弱相互作用，与BSA表现出疏水相互作用。所研究的钌化合物在体外和体内生物学测定中显示出有前景的结果。
