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Information Seminar Paper

Title

NEW COX-2 INHIBITOR DERIVATIVES AS POTENT ANTI-CANCER AGENTS

Writers

HAJABBASI M.A. | HEMAT A.

Pages

 Start Page | End Page

Abstract

 CANCER, WITH MORE THAN 11 MILLION DEATHS EVERY DAY, IS THE PRINCIPAL CAUSE OF MORTALITY IN ECONOMICALLY DEVELOPED COUNTRIES, AND THE SECOND LEADING CAUSE OF DEATH IN DEVELOPING COUNTRIES. THE WORLD HEALTH ORGANIZATION (WHO) PREDICTS THAT TWELVE MILLION OF ALL DEATHS WORLDWIDE WILL BE DUE TO CANCER BY 2030. THUS, DISCOVERING SUCCESSFUL TREATMENT FOR CANCER IS A VITAL OBJECTIVE. VARIOUS EXPERIMENTAL AND CLINICAL STUDIES PROPOSE THAT SELECTIVE CYCLOOXYGENASE (COX)-2 INHIBITORS, A SUBCLASS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS), HAVE THE POTENTIAL TO BE USED AS ANTI-CANCER AGENTS. CELECOXIB AS THE FIRST CYCLOOXYGENASE-2 SELECTIVE NO NSTEROIDAL INHIBITOR HAS BEEN APPROVED FOR THE TREATMENT OF ADULT ARTHRITIS. CELECOXIB ALSO EXHIBITED POTENT CHEMO PREVENTIVE ACTIVITY IN CHEMICAL CARCINOGEN INDUCED COLON, BLADDER, AND BREAST CANCERS. CELECOXIB HAS A 1, 2-DI-ARYL HETEROCYCLIC STRUCTURE AND SHOULD BE AN IDEAL LEAD COMPOUND FOR DEVELOPING NOVEL DERIVATIVES WITH POTENT ANTI-PROLIFERATIVE ACTIVITY. IN THIS REGARD, WE INVESTIGATED ANTICANCER EFFECT OF TWO COX-2 INHIBITOR DERIVATIVES IN AN IN-VITRO AND IN-VIVO MODELS. IN VITRO EXPERIMENTS INCLUDING CYTOTOXICITY ASSAY, FLOWCYTOMETRY, WESTERN BLOTTING AND ANNEXIN-V-PI ANALYSIS PERFORMED AGAINST MCF-7 AND K562 CELL LINES. ADDITIONALLY, BALB/C-DERIVED 4T1TUMORS WAS USED AS AN IN-VIVO MODEL. THE OBTAINED RESULTS SHOWED STRIKING ANTICANCER ACTIVITY OF THE TWO COX-2 DERIVATIVES USED IN OUR EXPERIMENTS. THESE RESULTS PROMPTED USE TO EVALUATE THE ANT IMETASTATIC ACTIVITY OF THE COMPOUNDS ON MDA-MB-231 CELLS. INTERESTINGLY, THE RESULTS WERE IN AGREEMENT WITH OUR PREVIOUS REPORTS SUGGESTING THESE COMPOUNDS AS CHEMOTHERAPEUTIC AGENTS WHICH CAN PREVENT METASTASIS IN BREAST CANCER. OF COURSE, OUR STUDIES WOULD SERVE AS THE GROUNDWORK FOR FURTHER STUDIES TO DEVELOP THE NEW COMPOUNDS.

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