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A novel combination of ruthenium polypyridyl complex, [Ru(dppz)2PiP]2+ and PARP inhibitor, NU1025 for cancer treatment
Yusoh N. A1, Haslina Ahmad2, Leong, S. W3.
Introduction: Ruthenium polypyridyl complex (RPC), [Ru(dppz)2PiP]2+ or RuPiP, where dppz = dipyridophenazine, and PiP = 2-phenylimidazo[4,5-f][1,10]phenantroline has been shown to exhibit anticancer activities by stalling the replication fork progression in human cancer cell line, causing DNA double-strand break (DSB) leading to the initiation of DNA damage response (DDR). Poly (ADP-ribose) polymerase (PARP) enzymes are activated in response to DNA damage thus, RuPiP may be advantageously combined with the inhibitors of PARP to improve its efficacy in cancer cell killing. This study was conducted to investigate the cytotoxic effects of RuPiP and selected PARP inhibitor, NU1025, alone or in combination in vitro and the possible combinations in order to achieve synergism against three different cancer cell lines. Methods: Cell viability was determined by MTT assay based on established method and the combination index (CI) values were calculated using Chou and Talalay method. Results: Here, we reported that the treatment with RuPiP alone led to dose-dependent decreases in the cell viability meanwhile NU1025 exhibited no toxicity as a single agent. The CI values (<0.9) were interpreted as synergism and our results showed that the combination of RuPiP and NU1025 gave synergistic effects on all three different cancer cell lines. Conclusion: These finding suggest promising benefits of combining RuPiP and NU1025 to optimize cancer treatment in further preclinical and clinical studies.
Affiliation:
- Universiti Putra Malaysia, Malaysia
- Universiti Putra Malaysia, Malaysia
- Universiti Putra Malaysia, Malaysia
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Indexation |
Indexed by |
MyJurnal (2021) |
H-Index
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3 |
Immediacy Index
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0.000 |
Rank |
0 |
Indexed by |
Scopus 2020 |
Impact Factor
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CiteScore (0.2) |
Rank |
Q4 (Medicine (all)) |
Additional Information |
SJR (0.144) |
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