Inhibitor of differentiation 1 (Id1) expression attenuates the degree of TiO2-induced cytotoxicity in H1299 non-small cell lung cancer cells.
The inhibitor of differentiation (Id) family of genes, which encodes negative regulators of basic helix-loop-helix transcription factors, has been implicated in diverse cellular processes such as proliferation, apoptosis, differentiation, and migration. However, the specific role of Id1 in titanium dioxide (TiO2)-induced lung injury has not been investigated. In the present study, we investigated whether TiO2 induces apoptosis in H1299 lung cancer cells and by which pathways. Based on the results of the LDH assay, dual staining with Annexin V-FITC and propidium iodide (PI), and RT-PCR analysis of apoptosis-related gene expression, TiO2 caused a dose- and time-dependent decrease in cell viability and appeared to involve both necrosis and apoptosis. Furthermore, Id1 expression was significantly reduced in TiO2-treated cells compared with control cells. To further investigate the functional role of Id1, cells were transduced with a recombinant adenovirus expressing Id1, and the effects on sensitivity to TiO2 were analyzed. Id1 overexpression led to the enhancement of cellular proliferation and reduced the sensitivity of H1299 cells to TiO2. Our results indicate that Id1 expression attenuates the degree of TiO2-induced cytotoxicity in lung cells.
Lee
Young Sook
YS
Toxicogenomics Team, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
Yoon
Seokjoo
S
Yoon
Hea Jin
HJ
Lee
Kyuhong
K
Yoon
Hyoun Kyoung
HK
Lee
Jeung-Hoon
JH
Song
Chang Woo
CW
D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011419:Propidium; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014025:Titanium / Q000633:toxicity*
D017304:Annexin A5; D004396:Coloring Agents; D005456:Fluorescent Dyes; D051798:Inhibitor of Differentiation Protein 1; C009495:titanium dioxide; D011419:Propidium; D012313:RNA; D014025:Titanium; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases; D016650:Fluorescein-5-isothiocyanate