2-Deoxyglucose and Newcastle Disease Virus Synergize to Kill Breast Cancer Cells by Inhibition of Glycolysis Pathway Through Glyceraldehyde3-Phosphate Downregulation

Al-Shammari, Ahmed Majeed; Abdullah, Amer Hasan; Allami, Zainab Majid; Yaseen, Nahi Y.

doi:10.3389/fmolb.2019.00090

Cited by 36 publications

(35 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The abnormality of aerobic glycolysis is considered as one of the tumor markers, and in BC, aerobic glycolysis can not only provide nutrition for cell proliferation but also help to promote cell proliferation and metastasis. 22 A previous study revealed that histone methyltransferase Set8 could regulate aerobic glycolysis by stabilizing HIF1α. 23 In our study, we also found that the inhibition of PRMT5 expression significantly suppressed the aerobic glycolysis of BCCs, which was the first time we found that PRMT5 could affect it of BCCs.…”

Section: Discussionmentioning

confidence: 99%

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

Han¹,

Wei²,

Wu³

2020

OTT

View full text Add to dashboard Cite

Objective: To explore the effects of protein arginine methyltransferase 5 (PRMT5) on the biological function of breast cancer cells (BCCs) by regulating the liver X receptor α (LXRα)/NF-κBp65 pathway. Methods: A total of 80 patients with breast cancer (BC) admitted to our hospital were collected, and 80 breast cancer tissue specimens and 80 corresponding tumor-adjacent tissue specimens were sampled from them for analysis. The reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the expression of PRMT5 mRNA in the sampled tissues, and the Western blot to determine the expression of LXRα and NF-κBp65 proteins in the tissues and cells. The patients were followed up to analyze their 3-year survival rate. Stable and transient overexpression vectors and inhibition vectors were constructed and transfected into BCCs. The cell counting kit-8 (CCK8), transwell, and flow cytometry were adopted to analyze the proliferation, invasion, and apoptosis of transfected cells, on which the effects of PRMT5 on LXRα and NF-κBp65 proteins were analyzed. Results: PRMT5 was highly expressed in BC patients, and LXRα was lowly expressed in them, which had a high diagnostic value. Patients with high expression of PRMT5 showed a poor prognosis, and the expression of PRMT5 was related to the tumor size, pathological stage, differentiation, and metastatic in BC patients. Overexpressed PRMT5 enhanced the cell proliferation, invasion, and glycolysis abilities, weakened apoptosis ability, further lowered expression of LXRα and increased expression of NF-κBp65, while inhibited PRMT5 caused opposite results in those aspects. Up-regulating the expression of LXRα suppressed the proliferation, invasion, and aerobic glycolysis of BCCs and promoted their apoptosis, while inhibiting it posed opposite effects. The rescue experiment revealed that down-regulating the expression of PRMT5 could counteract the promotion of downregulation of LXRα on proliferation, invasion and glycolysis of BCCs, and the nude mouse tumorigenesis test revealed that PRMT5 induced tumor on nude mice by mediating LXRα/NF-κBp65. Conclusion: Inhibition of the PRMT5 expression can accelerate apoptosis of BCCs and weaken their proliferation, invasion, and aerobic glycolysis through the LXRα/NF-κBp65 pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

Han¹,

Wei²,

Wu³

2020

OTT

View full text Add to dashboard Cite

show abstract

“…Furthermore, 2-DG induces apoptosis of neuroblastoma SK-N-BE (2) cells [ 176 ] and its chronic dietary administration inhibits tumor incidence in a mouse model of hepatocarcinogenesis [ 177 ]. Moreover, 2-DG synergizes with Newcastle disease virus to kill breast cancer cells to inhibit GA-3-P dehydrogenase [ 178 ], and increases the efficacy of Adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo [ 179 ].…”

Section: The Warburg Effect and Tumor Therapymentioning

confidence: 99%

“…It was also found that YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease [ 182 ]. YAP increases glycolysis [ 179 ] and supports the expression of Glut3, a known driver of a cancer stem cell phenotype, whose expression is elevated in cancer [ 18 , 182 ]. YAP/TAZ/TEAD and AP-1 form a complex that synergistically activates target genes controlling S-phase entry and mitosis [ 183 ].…”

Section: The Warburg Effect and Tumor Therapymentioning

confidence: 99%

The Warburg Effect 97 Years after Its Discovery

Pascale

Calvisi

Simile

et al. 2020

Cancers

211

128

View full text Add to dashboard Cite

The deregulation of the oxidative metabolism in cancer, as shown by the increased aerobic glycolysis and impaired oxidative phosphorylation (Warburg effect), is coordinated by genetic changes leading to the activation of oncogenes and the loss of oncosuppressor genes. The understanding of the metabolic deregulation of cancer cells is necessary to prevent and cure cancer. In this review, we illustrate and comment the principal metabolic and molecular variations of cancer cells, involved in their anomalous behavior, that include modifications of oxidative metabolism, the activation of oncogenes that promote glycolysis and a decrease of oxygen consumption in cancer cells, the genetic susceptibility to cancer, the molecular correlations involved in the metabolic deregulation in cancer, the defective cancer mitochondria, the relationships between the Warburg effect and tumor therapy, and recent studies that reevaluate the Warburg effect. Taken together, these observations indicate that the Warburg effect is an epiphenomenon of the transformation process essential for the development of malignancy.

show abstract

“…Furthermore, pyruvate dehydrogenase kinase inhibition showed to improve reovirus oncolytic anti-tumor efficacy in several cancer types [29]. We reported previously that 2DG would enhance oncolytic NDV against breast cancer cells through glycolysis inhibition by downregulation of glyceraldehyde3-phosphate (GAPDH) [30]. Here, we investigate using D-Mannoheptulose, a hexokinase inhibitor to increase breast cancer cells sensitivity to oncolytic NDV, and the proposed mechanisms of this combination using glycolysis products analysis in breast cancer cells NDV-mediated oncolysis correlates with the disturbance within the metabolism.…”

Section: Introductionmentioning

confidence: 99%

Hexokinase inhibition using D-Mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Most cancer cells exhibit increased glycolysis and use this metabolic pathway cell growth and proliferation. Targeting cancer cells' metabolism is a promising strategy in inhibiting cancer cell progression. We used D-Mannoheptulose, a specific hexokinase inhibitor, to inhibit glycolysis to enhance the Newcastle disease virus antitumor effect. Methods: Human breast cancer cells were treated by NDV and/or hexokinase inhibitor. The study included cell viability, apoptosis, and study levels of hexokinase enzyme, pyruvate, ATP, and acidity. The combination index was measured to determine the synergism of NDV and hexokinase inhibitor. Results: The results showed synergistic cytotoxicity against breast cancer cells by combination therapy but no cytotoxic effect against normal cells. The effect was accompanied by apoptotic cell death and hexokinase downregulation and inhibition to glycolysis products, pyruvate, ATP, and acidity. Conclusions: The combination treatment showed safe significant tumor cell proliferation inhibition compared to monotherapies suggesting a novel strategy for anti-breast cancer therapy through glycolysis inhibition by hexokinase downregulation.

show abstract

2-Deoxyglucose and Newcastle Disease Virus Synergize to Kill Breast Cancer Cells by Inhibition of Glycolysis Pathway Through Glyceraldehyde3-Phosphate Downregulation

Cited by 36 publications

References 42 publications

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

The Warburg Effect 97 Years after Its Discovery

Hexokinase inhibition using D-Mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells

Contact Info

Product

Resources

About