Glucose deprivation using 2-deoxyglucose and acarbose induce metabolic oxidative stress and apoptosis in female mice bearing breast cancer

Obaid, Qayssar A; Khudair, Khalisa Khadim; Al-Shammari, Ahmed Majeed

doi:10.1016/j.biochi.2022.01.007

Cited by 12 publications

(5 citation statements)

References 35 publications

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“…A recent report postulated that NDV induces ferroptosis in tumor cells exposed to nutrient deprivation (Kan et al, 2021). Moreover, ACA-induced glucose deprivation displays cleavage of caspase and caspase substrates, which induces apoptosis (Caro-Maldonado et al, 2010;Obaid et al, 2022). Also, GD-induced stress promotes both TRAIL-RD/DR2 and receptor-mediated apoptosis (Iurlaro et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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

Obaid

Al-Shammari

Khudair

2022

Front. Mol. Biosci.

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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.

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Section: Discussionmentioning

confidence: 99%

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

Obaid

Al-Shammari

Khudair

2022

Front. Mol. Biosci.

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“…Elevated blood glucose is also a risk factor for breast cancer and NSCLC [19]. It is likely that the combination of both reduced glucose levels and elevated ketone levels contributed to tumor management, as described previously [8,19].…”

Section: Discussionmentioning

confidence: 78%

“…Previous studies in mice and humans with brain cancer have shown that low blood glucose levels are associated with reduced brain tumor growth rate and better survival, while elevated glucose or hyperglycemia contributes to rapid tumor growth and poor patient survival [9,18]. Elevated blood glucose is also a risk factor for breast cancer and NSCLC [19]. It is likely that the combination of both reduced glucose levels and elevated ketone levels contributed to tumor management, as described previously [8,19].…”

Section: Discussionmentioning

confidence: 82%

Restricted Ketogenic Diet Therapy for Primary Lung Cancer With Metastasis to the Brain: A Case Report

Evangeliou¹,

Spilioti²,

Vassilakou³

et al. 2022

Cureus

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A high-fat and low-carbohydrate diet was administered as a complementary and alternative therapy to a 54year-old man suffering from non-small-cell lung cancer (NSCLC) with brain metastasis. Three months after the cessation of chemotherapy and radiotherapy, a ketogenic diet (KD) was initiated. This approach was an attempt to stabilize the disease progression after chemotherapy and radiotherapy. Computed tomography following radiation and chemotherapy showed a reduction in the right frontal lobe lesion from 5.5 cm × 6.2 cm to 4 cm × 2.7 cm, while the mass in the upper-right lung lobe reduced from 6.0 cm × 3.0 cm to 2.0 × 1.8 cm. Two years after KD initiation and without any other therapeutic intervention, the right frontal lobe lesion calcified and decreased in size to 1.9 cm × 1.0 cm, while the size of the lung mass further decreased to 1.7 cm × 1.0 cm. The size of the brain and lung lesion remained stable after nine years of KD therapy. However, dyslipidemia developed after this time which led to the discontinuation of the diet. No tumor relapse or health issues occurred for two years after the discontinuation of the diet. This case report indicates that the inclusion of ketogenic metabolic therapy following radiation and chemotherapy is associated with better clinical and survival outcomes for our patient with metastatic NSCLC.

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“…Generally, a moderate level of ROS favors tumor cell proliferation and survival, whereas excessive ROS usually causes oxidative stress and cell death [ 59 ]. Glucose deprivation and glycolysis inhibition induce excessive ROS production and decrease ATP production in glioma, breast, and colon cancer cells [ 60 , 61 ]. To adapt to harsh environments, solid tumor cells optimize nutrient utilization to fulfill their energy requirements and maintain redox homeostasis [ 39 – 41 ].…”

Section: Discussionmentioning

confidence: 99%

APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition

Zhao,

Cheng,

Yan

et al. 2024

Cell Commun Signal

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Background In addition to functioning as a precise monitoring mechanism in cell cycle, the anaphase-promoting complex/cyclosome (APC/C) is reported to be involved in regulating multiple metabolic processes by facilitating the ubiquitin-mediated degradation of key enzymes. Fatty acid oxidation is a metabolic pathway utilized by tumor cells that is crucial for malignant progression; however, its association with APC/C remains to be explored. Methods Cell cycle synchronization, immunoblotting, and propidium iodide staining were performed to investigate the carnitine palmitoyltransferase 1 C (CPT1C) expression manner. Proximity ligation assay and co-immunoprecipitation were performed to detect interactions between CPT1C and APC/C. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium, inner salt (MTS) assays, cell-scratch assays, and transwell assays and xenograft transplantation assays were performed to investigate the role of CPT1C in tumor progression in vitro and in vivo. Immunohistochemistry was performed on tumor tissue microarray to evaluate the expression levels of CPT1C and explore its potential clinical value. Results We identified CPT1C as a novel APC/C substrate. CPT1C protein levels exhibited cell cycle-dependent fluctuations, peaking at the G1/S boundary. Elevated CPT1C accelerated the G1/S transition, facilitating tumor cell proliferation in vitro and in vivo. Furthermore, CPT1C enhanced fatty acid utilization, upregulated ATP levels, and decreased reactive oxygen species levels, thereby favoring cell survival in a harsh metabolic environment. Clinically, high CPT1C expression correlated with poor survival in patients with esophageal squamous cell carcinoma. Conclusions Overall, our results revealed a novel interplay between fatty acid utilization and cell cycle machinery in tumor cells. Additionally, CPT1C promoted tumor cell proliferation and survival by augmenting cellular ATP levels and preserving redox homeostasis, particularly under metabolic stress. Therefore, CPT1C could be an independent prognostic indicator in esophageal squamous cell carcinoma.

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Glucose deprivation using 2-deoxyglucose and acarbose induce metabolic oxidative stress and apoptosis in female mice bearing breast cancer

Cited by 12 publications

References 35 publications

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

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

Restricted Ketogenic Diet Therapy for Primary Lung Cancer With Metastasis to the Brain: A Case Report

APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition

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