Shahsavar Farhad, Bozorgmehr Mahmood, Mirzadegan Ebrahim, Abedi Anita, Lighvan Zohreh Mehri, Mohammadi Fereshteh, Safari Nasser, Amani Vahid, Zarnani Amir-Hassan
Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Anticancer Agents Med Chem. 2016 Feb 11;16(3):393 - 403.
Cisplatin as a platinum (Pt)-based chemotherapeutic compound is commonly applied for the treatment of several types of cancer. Nonetheless, drug resistance and severe adverse effects have been observed upon using cisplatin. Here, we have explored the cytotoxicity of novel Pt-based compounds on several cancer cell lines.
Five synthetic Pt compounds as well as cisplatin were investigated by XTT assay to determine their cytotoxicity against cell lines originated from prostate, ovary, and breast cancers at different time periods at various concentrations. Additionally, the apoptosis rate in cell lines was determined using flow cytometry. Binding to DNA was investigated through spectrophotometric and viscometric studies.
With the exception of one compound, all of the Pt-complexes effectively killed the prostate cancer cell lines (i.e. PC-3 and DU 145). One compound, [Pt(2,2'- dipyridylamine)Cl4].DMF, was chosen as the most potent compound due to its high selective cytotoxic activity and its cytotoxicity was further tested and compared with that of cisplatin on SKOV-3, Caov-4, MDA-MB-231, and MCF7 cell lines. [Pt(2,2'-dipyridylamine)Cl4].DMF had a higher selective cytotoxic capacity in comparison with cisplatin at higher concentrations and longer culture periods. Furthermore, as related to apoptosis induction, treatment with [Pt(2,2'-dipyridylamine)Cl4 ].DMF was significantly more effective than that of cisplatin in five out of six examined cell lines. [Pt(2,2'-dipyridylamine)Cl4].DMF was shown to intercalate into DNA.
The current study introduced a novel Pt-based complex with highly selective and potent in vitro anti-tumor impacts superior to those of cisplatin, a conventional chemotherapeutic agent. [Pt (2,2'-dipyridylamine)Cl4].DMF could be regarded as a promising anti-tumor agent in future investigations.
顺铂作为一种基于铂（Pt）的化疗化合物，常用于治疗多种类型的癌症。然而，使用顺铂时会出现耐药性和严重的不良反应。在此，我们探讨了新型铂基化合物对几种癌细胞系的细胞毒性。
通过XTT试验研究了五种合成铂化合物以及顺铂在不同浓度、不同时间段对源自前列腺癌、卵巢癌和乳腺癌的细胞系的细胞毒性。此外，使用流式细胞术测定细胞系中的凋亡率。通过分光光度法和粘度测定法研究与DNA的结合情况。
除一种化合物外，所有铂配合物均能有效杀死前列腺癌细胞系（即PC-3和DU 145）。一种化合物[Pt(2,2'-二吡啶胺)Cl4].DMF因其高选择性细胞毒性活性而被选为最有效的化合物，并进一步测试了其细胞毒性，并与顺铂在SKOV-3、Caov-4、MDA-MB-231和MCF7细胞系上的细胞毒性进行了比较。在较高浓度和较长培养期下，[Pt(2,2'-二吡啶胺)Cl4].DMF与顺铂相比具有更高的选择性细胞毒性能力。此外，在凋亡诱导方面，在六种检测的细胞系中的五种中，用[Pt(2,2'-二吡啶胺)Cl4].DMF处理比顺铂显著更有效。[Pt(2,2'-二吡啶胺)Cl4].DMF显示可插入DNA。
本研究引入了一种新型铂基配合物，其具有高度选择性和强大的体外抗肿瘤作用，优于传统化疗药物顺铂。[Pt(2,2'-二吡啶胺)Cl4].DMF在未来的研究中可被视为一种有前景的抗肿瘤药物。
