Research Projects

Scientific rational and importance of the study We have established some novel ruthenium (Ru) compounds as antiplatelet agents. Remarkably, Ru compounds inhibited in vitro platelet aggregation and in vivo thrombotic platelet plug formation in mice. Several lines of evidences have found that activation of platelets and the coagulation system play a critical role in the progression of cancer. As cited above, Ru compounds inhibited platelet aggregation and thrombotic platelet plug formation we assumed that these types of Ru compounds may act as anticancer agents and partially proved by preliminary data. Hypothesis/model to be tested Objective-1: To characterize and check the purity of the newly synthesized ruthenium compounds. Hypothesis: Characterization and purity conformation of a newly synthesized compound is important for the drug development. Objectives-2: To test the cytotoxicity of Ru compounds against cancer cells and fix their IC50 values and examine their effect on extra cellular matrix (ECM) components-MMPs and TIMPs. Hypothesis: Evidence suggests that ECM components are active during cancer progression. Hence, inhibiting ECM components might be an attractive treatment strategy. MMPs are considered promising targets for cancer treatment. Objectives-3: To study the regulatory machinery of Ru-mediated anticancer effects via modulating extrinsic/intrinsic apoptosis, ROS and other molecules. Hypothesis: It is well known that anticancer agents can generate ROS for activating apoptotic signaling pathways. Therefore, development of anticancer agents for overproduction of ROS in cancer cells is a good strategy in cancer therapy. Objective-4: To examine the nuclear factor kappa B (NF-κB) and MAPKs pathway underlying the anticancer effect of Ru compounds Hypothesis: Tumor cell proliferation and apoptosis suppression are promoted by NF-kB/MAPK activity. Thus, the inhibition of NF-κB/MAPK pathway has beneficial for the treatment cancer. Objective-5: To assay antioxidant defense systems in order to examine their role in cancer treatment. Hypothesis: Antioxidants may provide some benefit when combined with certain types of chemotherapy in cancer patients. Objective-6: To evaluate the impact of Ru on lung metastatic tumor nodules and histological alterations in cancer induced mice. Hypothesis: Tumor histopathology plays important roles such as differentiating from other lesions, which cannot be substituted by imaging techniques or tumor markers. Significance to the field of Research Since there is no detailed mechanisms of Ru(II) complexes in regulating NF-κB/MAPK-mediated MMPs inhibition for cancer treatment, the designed proposal is very important to develop novel Ru based MMP inhibitors. Hence, low-cost and safe mettalo-drugs can be progressed and used as the source of medicines for the treatment of cancer patients as NF-κB/MMP inhibitors.