Restoring p53 Function and Silencing REV3L Suppresses the Cancerous Metabolic Phenotype in Cisplatin Treated Human Non-Small Lung Carcinoma Cells

Abstract

Lung cancer is one of the deadliest cancers in the world accounting for over one-quarter of all cancer-related deaths, but in many cases, the cancer can develop a resistance to the cisplatin-based chemotherapies. It is well known that cancer cells exhibit the Warburg effect and some studies have suggested that cancer cell metabolism may be linked to cisplatin resistance. In this study, the effects of tumor suppressor protein p53 and translesional synthesis protein REV3L are studied to relate DNA damage signaling and repair to cellular metabolism by using the fluorescence lifetime of the metabolic coenzyme NADH. It was found that simultaneously restoring function to p53 and silencing REV3L suppressed the cancerous metabolic phenotype and resulted in the greatest amount of cancer cell death. This study demonstrates a previously unrecognized relationship between p53 and REV3L in cellular metabolism and may lead to improvements in chemotherapy treatment plans that reduce cisplatin resistance in cancer cells.