Salvadora Persica(Miswak) Extract Inhibits Invasion of Oral Malignant Cells : In-vitro and In-silico Assessment

Background: Carcinogenesis is a multistep disease evolving from cells with unlimited proliferation, aborted death and acquired invasion potential. Intervention in each step may stop subsequent evolution. The most prevalent type of cancer in the oral cavity is squamous cell carcinoma (SCC). Mortality is due to invasion and spread of malignant cells to vital structures. Invasion is a crucial property gained by cancer cells via upregulation of a set of genes. In oral SCCs, there is an upregulation of matrix metalloproteinases (MMPs), particularly MMP-2, in stages of lymph node involvement. Research on MMP-2 expression in oral squamous cell carcinoma is, however, scarce. A significant part in dealing with cancer has been the use of medicinal plants. The majority of plant secondary metabolites' and their derivatives' uses have been focused on preventing cancer. Salvadora Persica known also as Miswak is a well reputable plant with known pharmacological impacts. Testing new anticancer drugs from natural sources for their cytotoxic action against human cancer cell lines (in vitro) or utilizing animals (in vivo) as model systems or in silico research led to the discovery of many of these compounds and their molecular mode of action. Therefore, documenting the molecular expression of MMP-2, an invasion protein, in OSCC is therefore of great value. Results: Miswak extract inhibited the production of MMP-2 protein in Hep-2 cells using ELISA assay. Molecular Docking proved that eight components of Salvadora Persica can bind efficiently to active sites in MMP-2 protein so inhibit its function. Conclusion: This work focuses for the first time on Miswak antiinvasive potential both in vitro and in silico. This research is a step for further preclinical and clinical applications trying to decrease the challenge of oral squamous cell carcinoma invasion and subsequent metastasis to surrounding as well as remote tissues.