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Cytotoxicity, radiosensitization, and chemosensitization of tumor cells by 2-deoxy-D-glucose in vitro
1Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India.
Abstract:
The glucose analog 2-deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolytic ATP production, is the most widely investigated metabolic inhibitor for targeting glucose metabolism. Besides depleting energy in cells, 2-DG has also been found to alter N-linked glycosylation leading to unfolded protein responses and induce changes in gene expression and phosphorylation status of proteins involved in signaling, cell cycle control, DNA repair, calcium influx, and apoptosis. Inhibition of cell proliferation and induction of apoptosis have been observed as cytotoxic effects in a wide variety of tumor cells in vitro, while sensitization of tumor cells to ionizing radiation and certain chemotherapeutic drugs is associated with enhanced mitotic as well as apoptotic cell death induced by the primary therapeutic agent. Therefore, there has been a considerable amount of interest in developing 2-DG as a therapeutic agent or adjuvant in the radiotherapy and chemotherapy of tumors.
Insights
2-deoxy-D-glucose (2-DG) targets cancer cell metabolism by inhibiting glucose uptake and ATP production. This metabolic inhibitor shows promise as a therapeutic agent or adjuvant in cancer treatment, enhancing chemotherapy and radiotherapy efficacy.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- 2-deoxy-D-glucose (2-DG) is a glucose analog investigated for its metabolic inhibitory effects.
- It targets glucose transport and ATP production, impacting cellular energy.
- 2-DG also influences N-linked glycosylation, protein folding, gene expression, and signaling pathways.
Purpose of the Study:
- To explore the multifaceted effects of 2-DG on cellular metabolism and function.
- To evaluate the potential of 2-DG as a therapeutic agent or adjuvant in cancer treatment.
- To understand 2-DG's role in sensitizing tumor cells to existing therapies.
Main Methods:
- Investigating 2-DG's impact on glucose metabolism and ATP production.
- Analyzing 2-DG's effects on N-linked glycosylation and the unfolded protein response.
- Evaluating cytotoxic effects (inhibition of proliferation, induction of apoptosis) in tumor cells.
- Assessing 2-DG's synergistic effects with ionizing radiation and chemotherapy.
Main Results:
- 2-DG depletes cellular energy by inhibiting glycolysis.
- It induces unfolded protein responses and alters gene expression and protein phosphorylation.
- Cytotoxic effects, including proliferation inhibition and apoptosis induction, were observed in various tumor cells.
- 2-DG sensitizes tumor cells to radiotherapy and chemotherapy, enhancing treatment outcomes.
Conclusions:
- 2-DG exhibits significant anti-cancer properties by targeting cellular metabolism.
- Its ability to induce apoptosis and inhibit proliferation makes it a potential therapeutic agent.
- 2-DG enhances the efficacy of conventional cancer treatments like radiation and chemotherapy.
- Further development of 2-DG as a therapeutic or adjuvant is warranted.
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