RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species

Qiong Wang; Wenshu Chen; Xiuling Xu; Bilan Li; Weiyang He; Mabel T. Padilla; Jun-Ho Jang; Toru Nyunoya; Shantu Amin; Xia Wang; Yong Lin

doi:10.1093/carcin/bgt143

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RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species

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RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species

Qiong Wang, Wenshu Chen, Xiuling Xu, Bilan Li, Weiyang He, Mabel T. Padilla, Jun-Ho Jang, Toru Nyunoya, Shantu Amin, Xia Wang, …

Carcinogenesis (New York), Vol.34(9), pp.2119-2128

09/01/2013

DOI: 10.1093/carcin/bgt143

PMID: 23633517

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Abstract

Cell survival signaling is important for the malignant phenotypes of cancer cells. Although the role of receptor-interacting protein 1 (RIP1) in cell survival signaling is well documented, whether RIP1 is directly involved in cancer development has never been studied. In this report, we found that RIP1 expression is substantially increased in human non-small cell lung cancer and mouse lung tumor tissues. RIP1 expression was remarkably increased in cigarette smoke-exposed mouse lung. In human bronchial epithelial cells (HBECs), RIP1 was significantly induced by cigarette smoke extract or benzo[a]pyrene diol epoxide (BPDE), the active form of the tobacco-specific carcinogen benzo(a)pyrene. In RIP1 knockdown HBECs, BPDE-induced cytotoxicity was significantly increased, which was associated with induction of cellular reactive oxygen species (ROS) and activation of mitogen-activated protein kinases (MAPKs), including c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38. Scavenging ROS suppressed BPDE-induced MAPK activation and inhibiting ROS or MAPKs substantially blocked BPDE-induced cytotoxicity, suggesting ROS-mediated MAPK activation is involved in BPDE-induced cell death. The ROS-reducing enzyme catalase is destabilized in an ERK- and JNK-dependent manner in RIP1 knockdown HBECs and application of catalase effectively blocked BPDE-induced ROS accumulation and cytotoxicity. Importantly, BPDE-induced transformation of HBECs was significantly reduced when RIP1 expression was suppressed. Altogether, these results strongly suggest an oncogenic role for RIP1, which promotes malignant transformation through protecting DNA-damaged cells against carcinogen-induced cytotoxicity associated with excessive ROS production.

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Title: Subtitle: RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species
Creators: Qiong Wang - Lovelace Respiratory Research Institute
Wenshu Chen - Lovelace Respiratory Research Institute
Xiuling Xu - Lovelace Respiratory Research Institute
Bilan Li - Lovelace Respiratory Research Institute
Weiyang He - Lovelace Respiratory Research Institute
Mabel T. Padilla - Lovelace Respiratory Research Institute
Jun-Ho Jang - Lovelace Respiratory Research Institute
Toru Nyunoya - Lovelace Respiratory Research Institute
Shantu Amin - Penn State Milton S. Hershey Medical Center
Xia Wang - Sichuan University
Yong Lin - Lovelace Respiratory Research Institute
Resource Type: Journal article
Publication Details: Carcinogenesis (New York), Vol.34(9), pp.2119-2128
DOI: 10.1093/carcin/bgt143
PMID: 23633517
ISSN: 0143-3334
eISSN: 1460-2180
Publisher: Oxford University Press
Number of pages: 10
Language: English
Date published: 09/01/2013
Academic Unit: Internal Medicine
Record Identifier: 9985214102402771

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