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Overexpression of oxidored-nitro domain containing protein 1 inhibits human nasopharyngeal carcinoma and cervical cancer cell proliferation and induces apoptosis: Involvement of mitochondrial apoptotic pathways.

Oxidored-nitro domain containing protein 1 (NOR1) is a novel member of the             nitroreductase family that was first isolated as a tumor suppressor gene from             human nasopharyngeal carcinoma (NPC). However, the role of NOR1 gene dysfunction             in human cancers has not been addressed. We analyzed the expression of NOR1 in             various human cancer and benign tissue specimens and found significant downregulation             in nine types of cancer compared with corresponding non-tumor tissues. The recombinant             expression vector pCDNA3.1-myc-his-NOR1 was constructed and transfected into human             NPC 6-10B nasopharyngeal cancer and HeLa cervical cancer (CCA) cells. We found             that stable NOR1 overexpression resulted in suppression of 6-10B and HeLa cell             proliferation and led to S phase cell cycle arrest. In addition, NOR1 upregulation             enhanced apoptosis in pCDNA3.1-myc-his-NOR1 stably transfected cells, and it also             altered the expression of proteins involved in the mitochondria-dependent apoptotic             pathway. Furthermore, we also found that the NOR1 protein is a cytoplasmic protein             that is partially localized in the mitochondria and endoplasmic reticulum. Therefore,             NOR1 is an important tumor suppressor gene associated with NPC and CCA and may             play antitumor roles by inhibiting proliferation, preventing colony formation,             and promoting the apoptosis of tumor cells via the mitochondrial-dependent apoptotic             pathway. However, the precise mechanism behind the NOR1 antitumor effects needs             to be investigated further.