In the present study, it was found that the ruthenium (II) imidazole

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Ruthenium-based complexes have been regarded as one of the most potential metal-based candidates for anticancer therapy. Herein, two ruthenium (II) methylimidazole complexes [Ru(MeIm)(4npip)] (complex 1) and [Ru(MeIm)(4mopip)] (complex 2) were synthesized and evaluated for their in vitro anticancer activities. The results showed that these ruthenium (II) methylimidazole complexes exhibited moderate antitumor activity comparable with cisplatin against A549, NCI-H460, MCF-7 and HepG2 human cancer cells, but with less toxicity to a human normal cell line HBE. Intracellular distribution studies suggested that complex 2 selectively localized in the mitochondria. Mechanism studies indicated that complex 2 caused cell cycle arrest at G0/G1 phase by regulating cell cycle relative proteins and induced apoptosis through intrinsic pathway, which involved mitochondrial dysfunction, reactive oxygen species (ROS) accumulation and ROS-mediated DNA damage. Further, studies by western blotting suggested that MAPK and AKT signaling pathways were involved in complex 2-induced apoptosis, and they were regulated by the level of ROS. Overall, these findings suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent in the treatment of cancers.

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Camptothecin (CPT) exerts very strong antitumor activities by suppressing the activity of DNA topoisomerase I, but its application is greatly limited owing to its low solubility and the instability of the active lactone form. To overcome this bottleneck, we prepared the novel camptothecin nanocolloids based on N-trimethyl chitosan (CPT-TMC) to efficiently administer CPT systemically. In this study, we investigated the antitumor activity of CPT-TMC against both colon cancer and lung cancer. In vitro cell experiments both CPT and CPT-TMC significantly inhibited the growth of CT26 cells and LL/2 cells, but no statistical difference was observed between CPT-TMC and CPT. In vivo studies, CPT-TMC more effectively inhibited tumor growth and prolonged survival time than CPT both in the CT26 colon carcinoma subcutaneous model and in the LL/2 Lewis lung carcinoma subcutaneous model. In addition, results of PCNA and CD31 immunohistochemical staining of tumor tissues also confirmed the improved antitumor effect of CPT-TMC. These findings suggest that N-trimethyl chitosan could increase the antitumor effect of CPT. Consequently, CPT delivery by N-trimethyl chitosan is a potential approach for effective treatment of cancer.