TARGETED INHIBITION OF CONSTITUTIVE AND INTERLEUKIN-6-INDUCIBLE STAT3 SIGNALING CASCADE FOR THE PREVENTION AND TREATMENT OF HEAD AND NECK SQUAMOUS CELL CARCINOMA

Abstract

DESPITE ADVANCES IN EARLIER DETECTION AND NOVEL THERAPIES FOR HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC), IT STILL REMAINS A MAJOR HEALTH CONCERN AND CAUSES MORE THAN 350,000 DEATHS ANNUALLY WORLDWIDE. NOVEL PHARMACOLOGICAL AGENTS THAT ARE SAFE AND CAN OVERCOME CHEMORESISTANCE ARE URGENTLY REQUIRED, AS THE THERAPEUTIC EFFICACIES OF CURRENTLY USED CHEMOTHERAPEUTIC AGENTS SUCH AS CISPLATIN, ARE OFTEN QUITE LIMITED. A NATURAL COMPOUND, GARCINOL HAS BEEN ANALYZED IN HNSCC CELL LINES AND XENOGRAFT MOUSE MODEL TO EVALUATE ITS ANTI-CANCER POTENTIAL. WE FOUND THAT GARCINOL COULD EXHIBIT SIGNIFICANT DIVERSE ANTI-CANCER EFFECTS BOTH IN VITRO AND IN VIVO, MEDIATED THROUGH THE MODULATION OF MULTIPLE PRO-INFLAMMATORY SIGNALING CASCADES (STAT3, NF-?B PATHWAYS). FURTHERMORE, GARCINOL POTENTIATED THE ANTI-CANCER ABILITY OF CONVENTIONAL CHEMOTHERAPY DRUG CISPLATIN. OVERALL, OUR STUDIES HIGHLIGHT THE GREAT POTENTIAL OF GARCINOL AS AN EFFECTIVE ANTI-CANCER AGENT AGAINST HNSCC.