Heme Oxygenase-1 via Transcriptional Activation of Nrf2 Attenuates Apoptosis in Lung Cancer Cells.
- Author:
Hak Ryul KIM
1
;
Eun Jung KIM
;
Ki Eun HWANG
;
So Young KIM
;
Seong Hoon PARK
;
Jung Hyun PARK
;
Hwi Jung KIM
;
Sei Hoon YANG
;
Eun Taik JEONG
Author Information
- Publication Type:Original Article
- Keywords: Heme oxygenase-1; Nrf2; Apoptosis; Lung cancer
- MeSH: Apoptosis*; Blotting, Western; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Cell Line; Cytoprotection; Heme Oxygenase-1*; Heme*; Luciferases; Lung Neoplasms*; Lung*; Prostate; RNA, Small Interfering; Sarcoma; Transcriptional Activation*; Transfection
- From:Journal of Lung Cancer 2006;5(1):39-46
- CountryRepublic of Korea
- Language:English
- Abstract: 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
