Prahlad V Raninga
Griffith University, Australia
Title: Cross-talk between two antioxidants, thioredoxin reductase 1 and heme oxygenase-1 and therapeutic implications in multiple myeloma
Biography
Biography: Prahlad V Raninga
Abstract
Multiple myeloma (MM) is characterized by an accumulation of abnormal clonal plasma cells in the bone marrow. Despite recent advancements in anti-myeloma therapies, MM remains an incurable disease with only a slight increase in the median survival rate to 5 years. Th erefore, more eff ective therapies are needed. Antioxidant molecules are up-regulated in many human cancers, correlating with tumor proliferation, survival and drug-resistance and therefore, have been suggested as potential therapeutic targets. Th is study investigated the cross-talk between two major antioxidant molecules, thioredoxin reductase 1 (TrxR1) and hemeoxygenase-1 (HO-1) and their therapeutic implications in MM. We found that TrxR1 levels are up-regulated in MM cells compared to normal cells. We therefore tested the eff ect of TrxR1 inhibition using a specifi c inhibitor, auranofi n, on MM cell growth. Although auranofi n signifi cantly inhibited TrxR1 activity at the lower concentrations, MM cell proliferation was only inhibited at the higher concentrations of auranofi n. Inhibition of TrxR1 activity up-regulated another oxidative stress-responsive protein HO- 1, which has been shown to act as a secondary anti-apoptotic protein. Inhibition of TrxR1 in conjunction with HO-1 signifi cantly inhibited MM cell growth and induced apoptosis. Th us, HO-1 acts as a secondary anti-apoptotic mechanism in MM. Results showed that TrxR1 regulates HO-1 via the Nrf2 signaling pathway. Th ese fi ndings indicate that TrxR1 alone or in conjunction with HO-1 may serve as an eff ective therapeutic target to treat MM. Hence, this research highlights how understanding the cross-talk between these antioxidant systems may help in designing more eff ective therapeutic strategies to cure MM.