Effects of ketamine, s-ketamine, and MK 801 on proliferation, apoptosis, and necrosis in pancreatic cancer cells

Abstract

BackgroundAdenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. The oncogenic potential of this type of cancer is mainly characterized by its extreme growth rate triggered by the activation of signaling cascades. Modern oncological treatment strategies aim at efficiently modulating specific signaling and transcriptional pathways. Recently, anti-tumoral potential has been proven for several substances that are not primarily used in cancer treatment. In some tumor entities, for example, administration of glutamate antagonists inhibits cell proliferation, cell cycle arrest, and finally cell death.To attain endogenic proof of NMDA receptor type expression in the pancreatic cancer cell lines PaTu8988t and Panc-1 and to investigate the impact of ketamine, s-ketamine, and the NMDA receptor antagonist MK 801 on proliferation, apoptosis, and necrosis in pancreatic carcinoma.MethodsCell proliferation was measured by means of the ELISA BrdU assay, and the apoptosis rate was analyzed by annexin V staining. Immunoblotting were also used.ResultsThe NMDA receptor type R2a was expressed in both pancreatic carcinoma cell lines. Furthermore, ketamine, s-ketamine, and MK 801 significantly inhibited proliferation and apoptosis.ConclusionsIn this study, we showed the expression of the NMDA receptor type R2a in pancreatic cancer cells. The NMDA antagonists ketamine, s-ketamine, and MK 801 inhibited cell proliferation and cell death. Further clinical studies are warranted to identify the impact of these agents on the treatment of cancer patients.

NMDA receptors are important regulators of pancreatic cancer and are potential targets for treatment

“…This is contrary to the finding reported by Malsy et al23 who failed to demonstrate the presence of GluN1 and GluN2B in PanC-1 cells, and report only the presence of GluN2A. We expect this failure to find GluN1 and GluN2B might reflect deficiencies of the commercial antibodies using the conditions employed by them.…”

Physiological Roles of Non-Neuronal NMDA Receptors

“…Clinically, serum glutamate positively correlates with cancer progression and invasiveness [128], and the protumor effects of glutamate appear to be largely mediated by NMDARs. NMDARs have been identified in a wide variety of tumor types and cancer cell lines (Table 2), and, regardless of subunit configuration, NMDAR blockade reduces both cancer cell proliferation and invasiveness across many different cancers [129][130][131][132][133][134][135][136][137]. While the precise mechanisms underpinning the NMDAR-mediated effects on proliferation are poorly understood, there are clues.…”

Ketamine induces reactive oxygen species and enhances autophagy in SV‐HUC‐1 human uroepithelial cells

“…C. Q. Wang et al () detected an increased expression of crucial autophagic proteins LC3 and Beclin‐1, which was induced by ketamine in traumatic brain injury. Malsy et al () verified that ketamine could induce autophagy in pancreatic cancer cells. Autophagy is a critical cellular mechanism in various physiological and pathological processes.…”