NEO 212 Shown To Downregulate Production of MGMT For Treatment Of Non-Small Cell Lung Cancer
conjugate downregulates O6-
methylguanin DNA methltransferase via
proteolysis in non-small cell lung cancer (NSCLC).
Authors: Xingguo Song1, Li Xie1,2, Minghui Chang2,3, Xinran Geng4, Xingwu Wang1, Thomas C. Chen5, Xianrang Song1,2
A study into the effectiveness of NEO 212, a conjugate formulation of Temozolomide (TMZ) and Peryllil Alcohol (POH) to downregulate the production of MGMT, an alkylating agent that is a determinant of cancer resistance to temozolomide, was conducted by NeOnc Technologies . The study showed demonstrated NEO 212 inhibited MGMT dependent on the proteasomal pathway and this inhibition is a significant factor in its toxic effect in the non-small cell lung cancer (NSCLC) cells.
In the study, MGMT protein expression was measured in four different NSCLC cells, including A549, SPC-A1, NCI-H460, and NCI-H520. Next, these endogenous MGMT proteins were subjected to 100 μM of NEO 212, TMZ + POH (100 μM TMZ plus 100 μM POH), TMZ–POH, or DMSO for 48 hours. The treatment resulted in endogenous MGMT protein downregulation compared to its individual constituents and their combination. Additional test also showed NEO 212 inhibited MGMT protein expression in other cancer-derived cells, including ovarian carcinoma-derived
cell A2780, human NPC-derived cell lines CNE2, and glioma-derived cell line T98G.
1 Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China, 2 Department of Clinical Laboratory, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China, 3 School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medicine Science, Jinan, Shandong, China., 4Maternity & Child Care Center of Dezhou, Dongdizhong Street 835#, Decheng District, Dezhou, Shandong, China 5Departments of Neurological Surgery and Pathology, University of Southern California, Los Angeles, CA, USA