Event Title
Anti-Myeloma Effect of Imidazole and Methyl Derivatives of a Synthetic Oleanane Triterpenoid 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic Acid (CDDO)
Location
Georgia
Start Date
16-5-2017 1:00 PM
Description
INTRODUCTION: Multiple myeloma (MM) is a plasma cell cancer characterized by accumulation of malignant cells preferentially in the bone marrow. The synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its imidazole derivative CDDO-Im and methyl derivative CDDO-Me have been reported with therapeutic potential in treating various cancers, including hematological cancers. The objective of this study is to determine if CDDO-Im and CDDO-Me inhibit growth and induce apoptosis of multiple myeloma cells. METHODS: Cultured MM cell lines RPMI 8226, U266 and NCI-H929 were exposed to CDDO-Im and CDDO-Me (0 ~ 0.5 μM) for 24, 48, or 72 hours, respectively. Cell viability was measured using Presto Blue assay. Apoptosis of RPMI 8226 cells after 24 hour incubation with CDDO-Im or CDDO-Me (0 ~ 0.5 μM) were determined through flow cytometric analysis and western blot analysis. RESULTS: Both CDDO-Im and CDDO-Me prevented proliferation of all MM cells examined in a dose and time dependent fashion. Increase of percentage of apoptotic cells was observed with increase of concentrations of both CDDO derivatives. Expression of caspase-3, a pro-apoptotic factor, was significantly altered in a pattern suggesting the occurrence of apoptosis. CONCLUSIONS: Both CDDO-Im and CDDO-Me inhibit growth of multiple myeloma cells in a dose and time-dependent manner possibly through induction of apoptosis. Further study is needed to elucidate the mechanism of anti-myeloma action of CDDO-Im and CDDO-Me.
Embargo Period
6-20-2017
Anti-Myeloma Effect of Imidazole and Methyl Derivatives of a Synthetic Oleanane Triterpenoid 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic Acid (CDDO)
Georgia
INTRODUCTION: Multiple myeloma (MM) is a plasma cell cancer characterized by accumulation of malignant cells preferentially in the bone marrow. The synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its imidazole derivative CDDO-Im and methyl derivative CDDO-Me have been reported with therapeutic potential in treating various cancers, including hematological cancers. The objective of this study is to determine if CDDO-Im and CDDO-Me inhibit growth and induce apoptosis of multiple myeloma cells. METHODS: Cultured MM cell lines RPMI 8226, U266 and NCI-H929 were exposed to CDDO-Im and CDDO-Me (0 ~ 0.5 μM) for 24, 48, or 72 hours, respectively. Cell viability was measured using Presto Blue assay. Apoptosis of RPMI 8226 cells after 24 hour incubation with CDDO-Im or CDDO-Me (0 ~ 0.5 μM) were determined through flow cytometric analysis and western blot analysis. RESULTS: Both CDDO-Im and CDDO-Me prevented proliferation of all MM cells examined in a dose and time dependent fashion. Increase of percentage of apoptotic cells was observed with increase of concentrations of both CDDO derivatives. Expression of caspase-3, a pro-apoptotic factor, was significantly altered in a pattern suggesting the occurrence of apoptosis. CONCLUSIONS: Both CDDO-Im and CDDO-Me inhibit growth of multiple myeloma cells in a dose and time-dependent manner possibly through induction of apoptosis. Further study is needed to elucidate the mechanism of anti-myeloma action of CDDO-Im and CDDO-Me.
Comments
First-place winner of Excellence in Research - Pharmaceutical Sciences award