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 (
Introduction: Combination therapy to treat cancer have been demanded due to the complexity of the disease and to prevent resistance mechanisms commonly found in classic chemotherapeutic methods. Recently, we have reported that [Ru(dppz)2(PIP)]2+ (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) (RuPIP) immediately stalls replication fork progression in HeLa human cervical cancer cells. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells. These discoveries indicate that this class of compounds merit further investigation as anticancer drugs, especially within combinational therapy roles. However, information pertaining to the effects of combining ruthenium compounds with existing chemotherapeutic drugs remain scarce. This study aimed to investigate the possible synergistic cytotoxic effects of using RuPIP in combination with cisplatin on different cancer cell lines. Methods: A549, MCF7, Hela and T24 cells were treated with different concentrations of RuPIP or cisplatin alone, as well as different combinations of these two agents at a fixed ratio 1:1 over the course of 72 hr to assess their individual and combination effects. Cell viability was analysed using MTT assay. The combination index (CI) was calculated based on the Chou Talalay Method. Results: Single-agent treatment at 72 hr with RuPIP or cisplatin led to dose-dependent decreases in the viability of the A549, MCF7, Hela and T24 cells at 72 hr. Furthermore, increasing the concentrations of the combinations up to four folds of half maximal inhibitory concentration (IC50) statistically decrease the cell survival rates of A549 and MCF7 cells thus, displayed synergistic effects. Conclusion: Treatment of MCF7 and A549 cells with a combination of RuPIP and cisplatin showed a synergistic effect and thus are promising as a combination therapy for cancer treatment.
Introduction: Ruthenium compounds are widely studied for its biological activity. However, potent ruthenium drugs often have limited bioavailability due to its poor aqueous solubility. In order to assist the preparation of these hydrophobic compounds, a carrier or drug delivery agent is often introduced. Herein, we encapsulated a hydrophobic ruthenium polypyridyl complex [Ru(dppz)PIP]2+, (dppz = dipyrido-[3,2-a:20,30-c]phenazine, PIP = 2-phenylimidazo[4,5-f][1,10] phenanthroline) in mesoporous silica nanoparticles (MSN). Methods: The MSN was synthesized by using ionic liquid 1-hexadecylphenanthrolinium as a novel template and have 833.99 m2/g in surface area. The cytotoxicity of the synthesized ruthenium complex, MSN and MSN-loaded ruthenium was studied on Hela and A549 cancer cell lines. Results: MSN was non-toxic at lower dosage (