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NAD(P)H: Quinone Oxidoreductase 1 Overexpression in Hepatocellular Carcinoma Potentiates Apoptosis Evasion Through Regulating Stabilization of X-linked Inhibitor of Apoptosis Protein

NAD(P)H: Quinone Oxidoreductase 1 Overexpression in Hepatocellular Carcinoma Potentiates Apoptosis Evasion Through Regulating Stabilization of X-linked Inhibitor of Apoptosis Protein

Wan-Yu Li, Hong-Zhong Zhou, Yao Chen, Xue-Fei Cai, Hua Tang, Ji-Hua Ren, Vincent Kam Wai Wong, Betty Yuen Kwan Law, Yong Chen, Sheng-Tao Cheng, Hai-Bo Yu, Hao-Yang Cai, Wei-Xian Chen, Ni Tang, Wen-Lu Zhang, etc.

Cancer Lett. 2019 Jun 1;451:156-167.

PMID: 30867140

Abstract:

NAD(P)H: quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme which is associated with poor prognosis in human breast, colon, lung and liver cancers. However, the molecular mechanisms underlying the pro-tumorigenic function of NQO1 remains unclear. This study investigated the function of NQO1 in the context of hepatocellular carcinoma (HCC) development. We found that NQO1 was frequently up-regulated in human liver cancer, and its high expression level was correlated with the tumor stage and low survival rate of HCC patients. Loss-of-function of NQO1 inhibited growth in HCC cells with increased apoptosis in vitro, and suppressed orthotopic tumorigenicity in vivo. Mechanistically, high level of NQO1 in HCC cells enhanced protein stability of X-linked inhibitor of apoptosis protein (XIAP) by increasing its phosphorylation at Ser 87. Reintroduction of wile type XIAP and the phospho-mimic mutants XIAPS87D significantly reversed NQO1 knock-down/out induced growth inhibition and apoptosis. In mouse model with orthotopically implanted hepatocarcinoma, NQO1 suppression and NQO1 inhibitor suppressed tumor growth and induced apoptosis. NQO1 plays an important role in sustaining HCC cell proliferation and may thus act as a potential therapeutic target in HCC treatment.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415148	DT Diaphorase (NQO1) human			Price

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