Demirci Selami, Doğan Ayşegül, Başak Türkmen Neşe, Telci Dilek, Çağlayan Ahmet B, Beker Mustafa Ç, Kiliç Ertuğrul, Özkan Ferda, Dede Bülent, Şahin Fikrettin
aDepartment of Genetics and Bioengineering, Faculty of Engineering bDepartment of Pathology, Faculty of Medicine, Yeditepe University cDepartment of Physiology, Faculty of Medicine, Istanbul Medipol University, Istanbul dDepartment of Pharmaceutical Toxicology, University of Inonu, Malatya eDepartment of Chemistry, Faculty of Sciences and Arts, Süleyman Demirel University, Isparta, Turkey.
Anticancer Drugs. 2017 Sep;28(8):869-879. doi: 10.1097/CAD.0000000000000528.
Prostate cancer is the second most common cancer among men and the leading cause of death after lung cancer. Development of hormone-refractory disease is a crucial step for prostate cancer progression for which an effective treatment option is currently unavailable. Therefore, there is a need for new agents that can efficiently target cancer cells, decrease tumor growth, and thereby extend the survival of patients in late-stage castration-resistant prostate cancer. In the current study, a novel heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used to evaluate anticancer activity against prostate cancer in vitro and in vivo. Cell proliferation and cytotoxicity were evaluated by cell viability, gene, and protein expression assays in vitro. Results showed that the heterodinuclear copper(II)Mn(II) complex-P85 combination decreased cell proliferation by upregulating the apoptotic gene expressions and blocking the cell proliferation-related pathways. Tramp-C1-injected C57/B16 mice were used to mimic a prostate cancer model. Treatment combination of Schiff base complex and P85 significantly enhanced the cellular uptake of chemicals (by blocking the drug transporters and increased life time), suppressed tumor growth, and decreased tumor volume steadily over the course of the experiments. Overall, heterodinuclear copper(II)Mn(II) complex-P85 showed remarkable anticancer activity against prostate cancer in in vitro and in vivo.
前列腺癌是男性中第二常见的癌症,也是仅次于肺癌的主要死因。激素难治性疾病的发展是前列腺癌进展的关键步骤,目前尚无有效的治疗选择。因此,需要能够有效靶向癌细胞、减少肿瘤生长,从而延长晚期去势抵抗性前列腺癌患者生存期的新药物。在本研究中,一种新型的异双核铜(II)锰(II)席夫碱配合物与P85联合使用,以评估其在体外和体内对前列腺癌的抗癌活性。通过体外细胞活力、基因和蛋白质表达测定来评估细胞增殖和细胞毒性。结果表明,异双核铜(II)锰(II)配合物 - P85组合通过上调凋亡基因表达和阻断细胞增殖相关途径来降低细胞增殖。注射了Tramp - C1的C57 / B16小鼠被用于模拟前列腺癌模型。席夫碱配合物和P85的联合治疗显著增强了化学物质的细胞摄取(通过阻断药物转运体并延长其寿命),抑制了肿瘤生长,并在实验过程中使肿瘤体积稳步减小。总体而言,异双核铜(II)锰(II)配合物 - P85在体外和体内均显示出对前列腺癌显著的抗癌活性。