Glucose Deprivation Induced by Acarbose and Oncolytic Newcastle Disease Virus Promote Metabolic Oxidative Stress and Cell Death in a Breast Cancer Model

Abstract

Cancer cells are distinguished by enhanced glucose uptake and an aerobic glycolysis pathway in which its products support metabolic demands for cancer cell growth and proliferation. Inhibition of aerobic glycolysis is a smart therapeutic approach to target the progression of the cancer cell. We employed acarbose (ACA), a particular alpha-glucosidase inhibitor, to induce glucose deprivation combined with oncolytic Newcastle disease virus (NDV) to enhance antitumor activity. In this work, we used a mouse model of breast cancer with mammary adenocarcinoma tumor cells (AN3) that were treated with ACA, NDV, and a combination of both. The study included antitumor efficacy, relative body weight, glucose level, hexokinase (HK-1) level by ELISA, glycolysis product (pyruvate), total ATP, oxidative stress (ROS and reduced glutathione), and apoptosis by immunohistochemistry. The results showed significant antitumor efficacy against breast cancer after treatment with combination therapy. Antitumor efficacy was accompanied by a reduction in body weight and glucose level, HK-1 downregulation, inhibition of glycolysis products (pyruvate), total ATP, induction of oxidative stress (increase ROS and decrease reduced glutathione), and apoptotic cell death. The findings propose a novel anti–breast cancer combination involving the suppression of glycolysis, glucose deprivation, oxidative stress, and apoptosis, which can be translated clinically.

2-Deoxyglucose, an Inhibitor of Glycolysis, Enhances the Oncolytic Effect of Coxsackievirus

“…In contrast, metformin and phenformin generally caused opposite effects on the oncolytic activity of CVB5. Similar results were recently shown by the Al-Shammari group for the Newcastle disease virus acting as an oncolytic towards breast cancer cells [ 78 , 79 ]. This group triggered glucose deprivation not only with 2DG [ 78 ] but also with acarbose which is an inhibitor of alpha-glucosidase and amylase [ 79 ].…”

“…Similar results were recently shown by the Al-Shammari group for the Newcastle disease virus acting as an oncolytic towards breast cancer cells [ 78 , 79 ]. This group triggered glucose deprivation not only with 2DG [ 78 ] but also with acarbose which is an inhibitor of alpha-glucosidase and amylase [ 79 ]. Another example is the use of dichloroacetate which promotes a shift from anaerobic glycolysis to oxidative phosphorylation for the enhancement of oncolysis by the measles virus towards GBM [ 80 ].…”

Evaluation of the in vitro and in vivo effect of liposomal doxorubicin along with oncolytic Newcastle disease virus on 4T1 cell line: Animal preclinical research

“…Moreover, a study designed by Obaid et al. ( 2022 ) demonstrated ROS induction by NDV as an antitumour mechanism. Our study showed increasing in ROS levels similar to the previous study.…”

Oncolytic Adenovirus, a New Treatment Strategy for Prostate Cancer

“…Currently, plenty of viruses have been used for oncolytic therapy, including adenovirus, herpes simplex virus type I (HSV-1) [ 4 ], Newcastle disease virus [ 5 ], measles virus [ 6 ], mumps virus [ 7 ], vaccinia virus [ 8 ], and vesicular stomatitis virus [ 9 ]. Two oncolytic viruses H101 and T-Vec have been approved for the treatment of cancer.…”