Identification of troglitazone responsive genes: induction of RTP801 during troglitazone-induced apoptosis in Hep 3B cells.
Troglitazone is an anti-diabetic agent that improves hyperglycemia by reducing peripheral insulin resistance in type II diabetic patients. Troglitazone has been shown to cause growth inhibition of various normal and cancerous cells. However, the molecular mechanism by which troglitazone affects the growth of these cancer cells remains unclear. Here, we report that troglitazone treatment of Hep 3B human hepatocellular carcinoma cells resulted in dose-dependent growth inhibition. Analysis of cell cycle distribution by flow cytometry showed that the number of apoptotic cells was increased in a dose-dependent manner in response to troglitazone treatment. cDNA microarray analysis showed a number of differentially expressed genes in response to troglitazone. Among the upregulated genes, hypoxia-inducible factor 1 (HIF-1)-responsive RTP801 was induced in a dose-dependent manner. We also observed HIF-1 accumulation by immnocytochemistry after troglitazone treatment. These results strongly suggest that RTP801 might be involved in troglitazone-induced apoptosis in Hep 3B cells.
Kim
Jin Oh
JO
Department of Immunology, Kyungpook National University, Daegu, Korea.
Kim
Ji Young
JY
Kwack
Mi Hee
MH
Hong
Su Hyung
SH
Kim
Moon Kyu
MK
Kim
Jung Chul
JC
Sung
Young Kwan
YK
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002839:Chromans / Q000009:adverse effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000009:adverse effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000077288:Troglitazone
D002839:Chromans; C469991:DDIT4 protein, human; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone