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Published on: June 9, 2023
Newcastle disease virus suppress glycolysis pathway and induce breast cancer cells death
Ahmed Ghdhban Al-Ziaydi1, Ahmed Majeed Al-Shammari2, Mohammed I Hamzah3
1Department of Medical Chemistry, College of Medicine, University of Al-Qadisiyah, Al Diwaniyah, Iraq.
Abstract:
Newcastle disease virus (NDV) can modulate cancer cell signaling pathway and induce apoptosis in cancer cells. Cancer cells increase their glycolysis rates to meet the energy demands for their survival and generate ATP as the primary energy source for cell growth and proliferation. Interfering the glycolysis pathway may be a valuable antitumor strategy. This study aimed to assess the effect of NDV on the glycolysis pathway in infected breast cancer cells. Oncolytic NDV attenuated AMHA1 strain was used in this study. AMJ13 and MCF7 breast cancer cell lines and a normal embryonic REF cell line were infected with NDV with different multiplicity of infections (moi) to determine the IC50 of NDV through MTT assay. Crystal violet staining was done to study the morphological changes. NDV apoptosis induction was assessed using AO/PI assay. NDV interference with the glycolysis pathway was examined through measuring hexokinase (HK) activity, pyruvate, and ATP concentrations, and pH levels in NDV infected and non-infected breast cancer cells and in normal embryonic cells. The results showed that NDV replicates efficiently in cancer cells and spare normal cells and induce morphological changes and apoptosis in breast cancer cells but not in normal cells. NDV infected cancer cells showed decreased in the HK activity, pyruvate and ATP concentrations, and acidity, which reflect a significant decrease in the glycolysis activity of the NDV infected tumor cells. No effects on the normal cells were observed. In conclusion, oncolytic NDV ability to reduce glycolysis pathway activity in cancer cells can be an exciting module to improve antitumor therapeutics.
Insights
Newcastle disease virus (NDV) effectively targets breast cancer cells, inducing apoptosis and significantly reducing their energy-producing glycolysis pathway. This suggests NDV as a promising candidate for novel antitumor therapies.
Area of Science:
- Oncology
- Virology
- Biochemistry
Background:
- Cancer cells exhibit elevated glycolysis for energy demands.
- Newcastle disease virus (NDV) shows potential in modulating cancer cell signaling and inducing apoptosis.
- Targeting cancer cell glycolysis is a potential antitumor strategy.
Purpose of the Study:
- To investigate the effect of oncolytic NDV on the glycolysis pathway in infected breast cancer cells.
- To assess NDV's impact on key glycolysis markers and cellular energy production.
- To evaluate NDV's specificity towards cancer cells versus normal cells.
Main Methods:
- Infection of breast cancer cell lines (AMJ13, MCF7) and normal REF cells with oncolytic NDV (AMHA1 strain) at various multiplicities of infection (moi).
- Assessment of cell viability (MTT assay), morphological changes (crystal violet staining), and apoptosis (AO/PI assay).
- Measurement of hexokinase (HK) activity, pyruvate, ATP concentrations, and pH levels to evaluate glycolysis inhibition.
Main Results:
- NDV efficiently replicated in cancer cells while sparing normal cells.
- NDV induced significant apoptosis and morphological changes in breast cancer cells but not in normal cells.
- NDV infection led to decreased HK activity, pyruvate and ATP concentrations, and acidity in cancer cells, indicating reduced glycolysis.
Conclusions:
- Oncolytic NDV effectively inhibits the glycolysis pathway in breast cancer cells.
- NDV demonstrates selective toxicity towards cancer cells.
- The ability of NDV to reduce cancer cell glycolysis presents a novel therapeutic avenue for cancer treatment.
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