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KMID : 0982820060050010039
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Journal of Lung Cancer
2006 Volume.5 No. 1 p.39 ~ p.46
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Heme Oxygenase-1 via Transcriptional Activation of Nrf2 Attenuates Apoptosis in Lung Cancer Cells
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Kim Hak-Ryul
Kim Eun-Jung
Hwang Jong-Yun
Kim So-Young
Park Seong-Hoon
Park Jung-Hyun
Kim Hui-Jung
Yang Sei-Hoon
Jeong Eun-Taik
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Abstract
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Purpose: Increasing evidences have indicated the critical role of HO-1 in cytoprotection and more diverse biological functions. HO-1 has been reported to stimulate tumor cell growth and proliferation. And several tumors, including renal cell carcinoma, prostate tumor, hepatoma, and sarcoma, express a high level of HO-1. Indeed, inhibition of HO-1 by using specific HO inhibitors demonstrated in vivo antitumor activity. However, the precise mechanism of HO-1 induction and signals in lung cancer is not clearly known yet. We aimed to analyze the role of HO-1, characterize the mechanism of HO-1 induction, the role of Nrf2 in the induction, and investigated whether inhibition of HO-1 may induce apoptosis in lung cancer cells.
Materials and Methods: Western blot and immunostaining analyses were performed to ascertain whether HO-1, Nrf2, and NFkB were expressed or not in various lung cancer cell lines. Apoptosis by HO-1 inhibition through siRNA transfection was measured by flow cytometric analysis and Western blot. And the expression of HO-1 by siRNA of Nrf2 and NFkB was examined by ARE-driven luciferase activity and Western blot.
Results: We demonstrated that HO-1 was expressed highly in A549 cells than other lung cancer cells. And A549 cells were transfected by HO-1 small interfering RNA (siRNA) induced apoptosis. Nrf2 siRNA, next, resulted in a decrease of HO-1 expression. However, NFkB siRNA had no influence on the expression of HO-1.
Conclusion: Increasing HO-1 expression in A549 cells may be resulted from the transcriptional activation of Nrf2, and inhibition of Nrf2-HO-1 pathway induces apoptosis. Therefore it provides new important insights into the possible molecular mechanism of the antitumor therapy.
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KEYWORD
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Heme oxygenase-1, Nrf2, Apoptosis, Lung cancer
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