A Novel Ruthenium-Fluvastatin Complex Downregulates SNCG Expression to Modulate Breast Carcinoma Cell Proliferation and Apoptosis via Activating the PI3K/Akt/mTOR/VEGF/MMP9 Pathway.

Abstract

Breast cancer is the most common cause of malignancy and cancer-related morbidity and death worldwide that requests effective and safe chemotherapy. Evaluation of metallodrug-based anticancer agents and statins as chemotherapeutics with fewer side effects is a largely unexplored research field. Synthesis and characterization of the ruthenium-fluvastatin complex were 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. 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 to modify p53 expressions to interfere with apoptosis in the carcinoma of the breast, stimulated by the intrinsic apoptotic path assisted by Bcl2 and Bax in vivo, yet at the same point, controlling the PI3K/Akt/mTOR/VEGF pathway, as obtained from western blotting, correlates with the MMP9-regulated tumor mechanisms. 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.

• Authors: Wei Liang, Junfeng Shi, Haiyan Xia, Xiaowei Wei
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 5537737 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 34221232 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Wei Liang et al.

Chemical References

• Neoplasm Proteins
• SNCG protein, human
• gamma-Synuclein
• Fluvastatin
• Ruthenium
• Proto-Oncogene Proteins c-akt
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Breast Neoplasms (drug therapy, genetics)
• Cell Proliferation
• Down-Regulation
• Female
• Fluvastatin (pharmacology, therapeutic use)
• Humans
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Neoplasm Proteins (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Ruthenium (pharmacology, therapeutic use)
• gamma-Synuclein (metabolism)