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3,3′‐diindolylmethane inhibits adipogenesis of 3T3‐L1 preadipocytes by proteosomal degradation of cyclin D1
Author(s) -
Seo Sang gwon,
Shin Seung ho,
Min Soyun,
Kwon Jung Yeon,
Kim KeeHong,
Lee Ki Won,
Lee Hyong Joo
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.581.15
Subject(s) - adipogenesis , cyclin d1 , 3t3 l1 , cell cycle , cyclin e , chemistry , cyclin , microbiology and biotechnology , cancer research , biology , cell , biochemistry , gene
3,3′‐diindolylmethane (DIM) is a major metabolites of indole‐3‐carbinol (I3C), abundant in Brassica vegetables, such as broccoli and cabbage. DIM has been reported to have various biological activities including chemopreventive activity. However, anti‐obesity activity of DIM are poorly understood. Here we reported that DIM, but not I3C, inhibited adipogenesis of 3T3‐L1 cells by activating proteosomal degradation of cyclin D1. In consistent with this, mRNA levels of various adipogenic marker genes such as PPARγ, C/EBPα and aP2 were suppressed by DIM, but not I3C. Through pin‐point assay, we showed that this inhibitory effect was most potent at the early stage of adipogenesis, so called mitotic clonal expansion (MCE) step. We also showed that DIM inhibited cell number increase and cell cycle progression at G1 phase, that is, DIM inhibited MCE of 3T3‐L1 cells. Since cell cycle was arrested at G1 phase, we showed protein level of cyclin D1 which has been reported to be important at G1 to S transition. Cyclin D1 protein levels were reduced by DIM treatment. However, cyclin D1 mRNA level was not changed by DIM treatment. With hypothesis that DIM may induce degradation of cyclin D1, we co‐treated MG132 with DIM. MG132 treatment restored DIM‐inhibited cyclin D1 protein expression. Taken together, we concluded that DIM inhibited adipogenesis of 3T3‐L1 cells possibly by inducing degradation of cyclin D1.