Trans, trans-2,4-decadienal induced cell proliferation via p27 pathway in human bronchial epithelial cells.
Lung cancer is the leading cause of cancer deaths worldwide. Epidemiological studies have shown that exposure to cooking oil fumes (COF) is a risk factor for lung cancer. Trans, trans-2,4-decadienal (tt-DDE), a dienaldehyde, is abundant in heated oils and COF. Previously, we found that long-term exposure (45 days) to a sub-lethal dose (1 microM) of tt-DDE significantly increased growth of human bronchial epithelial cells (BEAS-2B). Aims of this study are to understand the mechanism of tt-DDE-induced cell proliferation and possible protective effects of antioxidant, vitamin C and N-acetylcysteine (NAC) in BEAS-2B cells. Utilizing the real-time RT-PCR and Western immunoblotting, we found that p27 mRNA and protein levels were significantly increased by 1 microM tt-DDE treatment. Co-treatment with vitamin C or NAC partially prevented tt-DDE-induced cell proliferation. In addition, the downstream targets of p27, including CDK4, cyclin D1 and phosphorylated-Rb proteins, increased in 1 microM tt-DDE-treated cells and these changes were prevented by NAC co-treatment. Therefore, these results suggest that tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D1 protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis.
Chang
Yun-Ching
YC
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
Lin
Pinpin
P
D000111:Acetylcysteine / Q000494:pharmacology; D000447:Aldehydes / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
D000447:Aldehydes; D000975:Antioxidants; D018076:DNA, Complementary; D017382:Reactive Oxygen Species; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; C057349:2,4-decadienal; D051358:Cyclin-Dependent Kinase 4; D001205:Ascorbic Acid; D000111:Acetylcysteine