Effect of mollugin on apoptosis and adipogenesis of 3T3‐L1 preadipocytes

Abstract

The effect of mollugin, isolated from the roots of Rubia cordifolia L., on cell viability, apoptosis and adipogenesis in 3T3-L1 preadipocytes was investigated. The inhibitory effect of mollugin (40-60 µM) on cell viability was more significant in differentiated adipocytes than in 3T3-L1 preadipocytes. In 3T3-L1 cells, the cytotoxicity of mollugin was accompanied by apoptotic events including mitochondrial membrane potential (Δψm) loss and activation of caspase-9, -3 and -7, leading to PARP degradation. Although the presence of 20 µM mollugin during induced adipocytic differentiation of 3T3-L1 cells for 6 days failed to affect the cell viability, it could almost completely abrogate the differentiation-associated morphology change and intracellular lipid accumulation. A similar level of inhibition was observed, when 20 µM mollugin was present during the early stage (D0-D2) of the differentiation period. In addition, the expression of C/EBPα, PPARγ1 and PPARγ2 was significantly down-regulated. The presence of 20 µM mollugin during either middle stage (D2-D4) or late stage (D4-D6) of the differentiation period, however, caused the inhibition to a lesser extent. These results indicated that mollugin at high concentrations (40-60 µM) exerted cytotoxicity via inducing apoptosis, whereas mollugin at a low concentration (20 µM) suppressed adipocytic differentiation without exerting cytotoxicity in 3T3-L1 preadipocytes.