A Novel Platinum-based Compound with Preferential Cytotoxic Activity against a Panel of Cancer Cell Lines

Author(s): Farhad Shahsavar, Mahmood Bozorgmehr, Ebrahim Mirzadegan, Anita Abedi, Zohreh Mehri Lighvan, Fereshteh Mohammadi, Nasser Safari, Vahid Amani, Amir-Hassan Zarnani.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 16 , Issue 3 , 2016

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Abstract:

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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 antitumor agent in future investigations.

Keywords: Chemotherapy, cisplatin, cytotoxicity, platinum-based compounds, tumor.

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Article Details

VOLUME: 16
ISSUE: 3
Year: 2016
Page: [393 - 403]
Pages: 11
DOI: 10.2174/1871520615666150807104228
Price: $58

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