Statins of gastric cancer, reduce cell migration

Statins are-3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMG-COAR) inhibitors lead to inhibit cholesterol synthesis and reduction of the downstream intermediate products that involve in carcinogenesis such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) .Statins include :- lovastatin , simvastatin ,atrovastatin ,flavastatin , pravastatin and rosuvastatin calcium. Statins used as hypocholesterolemic drugs in treatment of dyslipidemia , prevention cardiovascular disease, prevent development atherosclerosis , decrease low-density lipoprotein (LDL) , stroke myocardial injury and mortality .

There is multi-effect of statins as anti-inflammatory effect and anti-cancer effect and reduce cancer risk by  firstly ,  decrease level of cholesterol that tumor cells need it in development and expansion . Secondly , prevent oncogenic proteins (Ras,Rho,Rac, and Rab) activation . Statins reduce risk of gastric cancer, reduce cell migration and colony forming of prostate cancer-3 cells in prostate cancer , pancreatic cancer , esophagus cancer , hepatocellular carcinoma, lung cancer, colon cancer , colorectal cancer , improved survival in ovarian cancer and act as anew possible therapy in breast cancer  , in DVT( Deep Vein Thrombosis) and PE (Pulmonary embolism) patients statins have protective influence. Statins inhibit angiogenesis , tumor growth , invasion and metastasis , induce apoptosis ,reduce adhesion ,E selectin and matrix metalloproteinase -9 (MMP-9).In CLL patients statin and aspirin enhance cell apoptosis in addition statins improve response in chemotherapy.

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Moreover , Statins reduce risk of hematological malignancies ,f non-hodgkin lymphoma(NHL), multiple myeloma (MM) also induce apoptosis in CLL ,ALL,AML , MM and IM-9 lymphoblast .Because  the anti-leukemic effect of statins.   Wiskott-Aldrch Syndrom (WAS) is a rare X-linked recessive disorder caused by mutations in the gene for the WAS protein (WASP). WAS characterized by thrombocytopenia, small platelet size, autoimmunity and an increased risk of malignancies. WASP family contain WASP protein and N-WASP also WAVE proteins (WASP-family veprolin-homologous protein) family contain WAVE1,WAVE2 andWAVE3.

WASP proteins present only in hematopoietic cell but the rest of WASP family and WAVE proteins expressed in different tissue in addition expressed  in the cytoplasm of hematopoietic cells.WASP/WAVE proteins are scaffolds link upstream signals to activate actin- related protein 2 and 3 complex (ARP2/3) via binding with Veprolin/Cofilin/Acidic domain at  C terminus leading to initiate polymerization of actin cytoskeleton that required for other pathological modification like cell shap and morphology ,enhance cytokines , cell motility and progression and metastasis for cancer . The WASP/WAVE proteins work as downstream effectors to GTPase (Rho,RAS,Cdc42) that control actin polymerization and involve in cell motility and proliferation in addition WAVE proteins wok as downstream of Rac to induce formation of plasma membrane protrusion known as fillopodia and lamellipodia which known as invadpodia in cancer cell. Both Rac and Cdc-92 active nucleation- promoting factors (NPF) that consist of WASP,NWASP,WAVE1,WAVE2,WAVE3,WASH,WHAMM,JMY.  WAVE proteins play role in cell migration,  invasion , adhesion , motility and metastasis that lead to poor prognosis So WAVE proteins identified as prognostic marker or target for treatment and drug development that will affect on WAVE signaling pathway.

               

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