Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/79382
Title: IDENTIFICATION OF A NOVEL AGENT THAT CAN SUPPRESS PROLIFERATION, INDUCE APOPTOSIS AND OVERCOME CHEMORESISTANCE IN MULTIPLE MYELOMA
Authors: RADHAMANI KANNAIYAN
Keywords: Multiple myeloma, celastrol, apoptosis, proliferation, STAT3, NF-κB.
Issue Date: 5-Aug-2013
Source: RADHAMANI KANNAIYAN (2013-08-05). IDENTIFICATION OF A NOVEL AGENT THAT CAN SUPPRESS PROLIFERATION, INDUCE APOPTOSIS AND OVERCOME CHEMORESISTANCE IN MULTIPLE MYELOMA. ScholarBank@NUS Repository.
Abstract: MULTIPLE MYELOMA (MM), A B CELL MALIGNANCY STILL REMAINS INCURABLE, IN SPITE OF VARIOUS ADVANCES IN TREATMENT MODALITIES. STAT3 AND NF-KB TRANSCRIPTION FACTORS PLAY A CRUCIAL ROLE BOTH IN THE PATHOGENESIS AND PROGRESSION OF MM. IN THIS STUDY, WE DEMONSTRATE THAT CELASTROL, A QUINONE METHIDE TRITERPENOID DERIVED FROM CHINESE MEDICINAL PLANT TRIPTERYGIUM WILFORDII CAN SUPPRESS PROLIFERATION, INDUCE APOPTOSIS, INHIBIT MIGRATION AND INVASION AS WELL AS SYNERGISTICALLY ENHANCE APOPTOSIS INDUCED BY BORTEZOMIB AND THALIDOMIDE IN MM CELLS. MOREOVER, CELASTROL ABROGATED STAT3 AND NF-KB ACTIVATION PATHWAYS AND DOWN-REGULATED THE EXPRESSION OF VARIOUS ONCOGENIC GENE PRODUCTS INVOLVED IN MM PROGRESSION. WE ALSO PROVIDE EVIDENCE TO SUGGEST THAT QUINONE METHIDE MOIETY OF CELASTROL MAY BE CRITICAL FOR ITS OBSERVED STAT3 INHIBITORY EFFECTS IN MM CELLS. IN HUMAN MM XENOGRAFT MOUSE MODEL, CELASTROL ALSO POTENTIATED BORTEZOMIB-INDUCED INHIBITION OF TUMOR GROWTH THROUGH THE DOWNREGULATION OF STAT3 AND NF-
URI: http://scholarbank.nus.edu.sg/handle/10635/79382
Appears in Collections:Ph.D Theses (Open)

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