Abstract
One of the "hallmarks of cancer" is altered energy metabolism, which is increased glycolysis in cancer cells, the primary source of energy that uses this metabolic pathway to generate ATP. Oncolytic virotherapy with aerobic glycolysis inhibitor smart therapeutic approach to induce apoptosis in cancer cells. The current study aimed to use the 2-Deoxyglucose (2DG), a specific glycolysis inhibitor, to enhance the Newcastle disease virus (NDV). In this study, a mouse model of breast cancer allograft with mammary adenocarcinoma tumor cells (AN3) was used and treated with 2DG, NDV, and a combination of both. Anti-tumor efficacy and glycolysis analysis (hexokinase -1 (HK-1), pyruvate, and ATP) were determined. The induction of oxidative stress was investigated by reactive oxygen species (ROS) and total glutathione assay examination. Apoptosis induction was investigated using immunohistochemistry (cleaved Caspase-3) and histopathology. The result showed that combination therapy enhances anti-tumor efficacy (decrease in relative tumor volume and increase in tumor growth inhibition) of NDV against breast cancer. This effect was accompanied by a reduction in HK-1 concentration, pyruvate, and ATP (glycolysis products). Moreover, NDV+2DG therapy induces oxidative stress (decreases total glutathione and increases ROS). Immunohistochemistry and histopathological examination showed the apoptotic area in tumor tissues in treated groups. In conclusion, the present study found that the combination therapy could be considered as an effective cancer therapy through induction of glycolysis inhibition, oxidative stress, and apoptosis selectively in cancer cells.
Highlights
Cancer cells use a variety of strategies to proliferate and invade other tissues, including apoptosis avoidance, resistance to growth inhibitors, independence from growth signals, unlimited replication potential, chronic inflammation induction, genetic instability, immune escape, angiogenesis, and changes in cell metabolisms [1, 2]
On the eighteenth day of the experiment, a significant (P
It relies on aerobic glycolysis to avoid oxidative phosphorylation and utilize high quantities of glucose foranabolic processes [24]
Summary
Cancer cells use a variety of strategies to proliferate and invade other tissues, including apoptosis avoidance, resistance to growth inhibitors, independence from growth signals, unlimited replication potential, chronic inflammation induction, genetic instability, immune escape, angiogenesis, and changes in cell metabolisms [1, 2]. NDV exhibits three mechanisms to kill tumor cells: apoptosis induction, virus replication in cancer cells leading to cytolysis, and specific immune stimulation against cancer cells through tumor cells surface antigenic modification by virus infection [11,12,13]. This study investigated using 2DG, a hexokinase inhibitor to synergize oncolytic NDV for inducing metabolic oxidative stress, and study mechanisms action of this combination through glycolysis products analysis and apoptosis in breast cancer tissue
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
