Cetin Yuksel, Adiguzel Zelal, Polat Hivda U, Akkoc Tolga, Tas Arzu, Cevatemre Buse, Celik Gokalp, Carikci Baris, Yilmaz Veysel T, Ulukaya Engin, Acilan Ceyda
aTUBITAK, Marmara Research Center, Genetic Engineering and Biotechnology Institute bTUBITAK, TUSSIDE, Turkish Institute of Management Sciences Gebze/Kocaeli cDepartment of Biology dDepartment of Chemistry, Faculty of Arts and Sciences, Uludag University, Bursa eDepartment of Clinical Biochemistry, School of Medicine, Istinye University, Istanbul, Turkey.
Anticancer Drugs. 2017 Sep;28(8):898-910. doi: 10.1097/CAD.0000000000000531.
The main aim of this study is to assess the safety and antitumor efficacy of a palladium(II) (Pd)-saccharinate complex with terpyridine. To characterize the Pd(II) complex in vitro, its cytotoxicity was evaluated using a water-soluble tetrazolium salt cell viability assay and the mechanism of cell death was assessed by DNA fragmentation/condensation and live cell imaging analyses. The antitumor efficacy and safety of the Pd(II) complex in-vivo were examined by analyzing reduction in tumor size, changes in body and organ weight, histopathological analysis of liver, kidney, and tumor sections, and biochemical analysis of serum in C57BL/6 mice. Our results showed that the Pd(II) complex was more cytotoxic to cancer cells than noncancer cell lines and caused cell death through apoptotic pathways. The treatment of the Pd(II) complex in tumor-bearing mice effectively reduced the tumor size at half the dose used for cisplatin. The Pd(II) complex appeared to exert less liver damage than the cisplatin-based complex on changes in the hepatic enzymes levels in the serum. Hence, the complex appears to be a potential chemotherapeutic drug with high antitumor efficacy and fewer hepatotoxic complications, providing an avenue for further studies.
本研究的主要目的是评估一种钯（II）（Pd）-糖精与三联吡啶络合物的安全性和抗肿瘤疗效。为了在体外表征该Pd（II）络合物，使用水溶性四氮唑盐细胞活力测定法评估其细胞毒性，并通过DNA片段化/凝聚和活细胞成像分析评估细胞死亡机制。通过分析C57BL/6小鼠的肿瘤大小减小情况、体重和器官重量变化、肝脏、肾脏和肿瘤切片的组织病理学分析以及血清生化分析，研究了该Pd（II）络合物在体内的抗肿瘤疗效和安全性。我们的结果表明，该Pd（II）络合物对癌细胞的细胞毒性比对非癌细胞系更强，并通过凋亡途径导致细胞死亡。在荷瘤小鼠中使用该Pd（II）络合物进行治疗，在使用顺铂剂量一半的情况下有效地减小了肿瘤大小。该Pd（II）络合物在血清肝酶水平变化方面对肝脏的损伤似乎比基于顺铂的络合物更小。因此，该络合物似乎是一种具有高抗肿瘤疗效和较少肝毒性并发症的潜在化疗药物，为进一步研究提供了一条途径。
