Title:A Novel Platinum-based Compound with Preferential Cytotoxic Activity against a Panel of Cancer Cell Lines
VOLUME: 16 ISSUE: 3
Author(s):Farhad Shahsavar, Mahmood Bozorgmehr, Ebrahim Mirzadegan, Anita Abedi, Zohreh Mehri Lighvan, Fereshteh Mohammadi, Nasser Safari, Vahid Amani and Amir-Hassan Zarnani
Affiliation:Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Keywords:Chemotherapy, cisplatin, cytotoxicity, platinum-based compounds, tumor.
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.
