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

oncology reports

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