In this study, Neonc Technologies Holdings, Inc. showed that the cytotoxicity effects of its patented NEO212 compound Nasopharyngeal carcinoma (NPC) could inhibit NPC cell proliferation, and cause G2/M arrest and DNA damage. NEO212 is Neonc’s patented conjugated formulation of Temozolomide with Neonc’s highly purified Perillyl Alcohol. Temozolomide is a chemotherapy drug used primarily to treat certain types of brain tumors, including glioblastoma multiforme (GBM) and anaplastic astrocytoma. It belongs to a class of medications known as alkylating agents, which work by damaging the DNA of cancer cells, thereby preventing them from dividing and growing. The drug is known for its ability to cross the blood-brain barrier, which makes it particularly effective in treating brain tumors. 

NPC is a type of cancer that originates in the nasopharynx, which is the upper part of the throat located behind the nose. This region connects the back of the nose to the back of the mouth and is situated just above the soft part of the palate and the base of the skull. The 5-year survival rate for NPC depends upon how far the cancer has spread. For patients with localized NPC, cancer confined to the nasopharynx, the 5-year survival rate is generally high, ranging from 70% to 90%. For those with regional NPC that has spread to nearby lymph nodes, the 5-year survival rate decreases to 60% to 80%. For patients whose NPOC has spread to distant parts of the body, the 5-year survival rate drops to 30% to 50%.

In the study, NEO212 triggered apoptosis in NPC cells via significant activation of caspase-3 and poly(ADPribose) polymerase (PARP). Importantly, NEO212-induced cell death was found to be associated with (i) the loss of inner mitochondrial membrane potential (ΔΨm) and release of mitochondrial Cytochrome c, (ii) the increase in ROS generation, and (iii) the activation of stress-activated protein kinases (SAPK)/c-Jun N-terminal kinases (JNK) signaling pathway. The generation of ROS in response to NEO212 seems to play a crucial role in the cell death process since the blockage of ROS production using the antioxidant N-acetyl-L-cysteine or catalase reversed the NEO212- induced JNK activation, DNA damage, and cancer cell apoptosis. These results provide the rationale for further research and preclinical investigation of the antitumor effect of TMZ-POH against human NPC.

Read The Paper

The therapeutic effect of TMZ-POH on human nasopharyngeal carcinoma
depends on reactive oxygen species accumulation

Authors: Li Xie^1,*, Xingguo Song^1,*, Wei Guo², Xingwu Wang¹, Ling Wei¹, Yang Li¹, Liyan Lv¹, Weijun Wang³, Thomas C. Chen³, Xianrang Song¹

¹Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong Province, China
² Ultrasound Diagnosis Department, Shandong Cancer Hospital and Institute, Jinan, Shandong Province, China
³Department of Neurological Surgery and Pathology, University of Southern California, Los Angeles, CA, United States of America
^*These authors contributed equally to this work