A Novel Ruthenium Fluvastatin Complex Downregulates SNCG Expression to Modulate Breast Carcinoma Cell Proliferation and Apoptosis Via Activating PI3K/Akt/mTOR/VEGF/ MAP Kinase Pathway

Abstract Background: Breast cancer is the most common cause of malignancy and cancer related morbidity and death worldwide that requests effective and safe chemotherapy. Evaluation of metallo drug based anticancer agents and statins as chemotherapeutics with fewer side effects is largely unexplored research fieldsMethods: The synthesis and characterization of Ruthenium fluvastatin complex was achieved using multiple spectroscopic techniques and thus further examined to evaluate its chemotherapeutic prospects in both MDA-MB-231 and MCF-7 cancer lines and eventually in vivo models of DMBA induced mammary carcinogenesis in rodents. The viability of cells was tested using MTT assay. The apoptotic assay in cell lines was analyzed by flow cytometry. Western blot technique and immunohistochemical approach were used to investigate complex induced signaling pathways. TUNEL assay had predicted in-vivo apoptosis.Results: Our studies indicate that the metal and ligand chelation was materialized by the ligand's functional groups of carbonyl (= O) oxygen and hydroxyl (-OH) and the complex has been observed to be crystalline and able to chelate with CT-DNA. The complex was able to reduce cell proliferation and activate apoptotic events in breast carcinoma cell lines MCF-7 and MDA-MB-231. In addition, the complex was able modify p53 expressions to interfere with apoptosis in the carcinoma of the breast, stimulated by the intrinsic apoptotic path assisted by Bcl2 and Bax, yet at the same point controlling the PI3K / Akt / mTOR pathway correlated with MMP9 regulated tumor mechanisms.Conclusion: Our research reveals that ruthenium-fluvastatin chemotherapy may disrupt, rescind or interrupt breast carcinoma progression by modifying intrinsic apoptosis as well as the antiangiogenic cascade, thereby taking the role of a potential candidate in cancer therapy for the immediate future.