Glycolysis-related gene induction and ATP reduction during fractionated irradiation

Goetze, Kristina; Meyer, Sandra S.; Yaromina, Ala; Zips, Daniel; Baumann, Michaël; Mueller‐Klieser, Wolfgang

doi:10.1007/s00066-013-0371-9

Cited by 12 publications

(2 citation statements)

References 20 publications

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“…For example, ATP-dependent chromatin remodeling complexes in double-strand break (DSB) repair and poly ADP-ribose polymerase (PARP) activity are ATP dependent. [29][30][31][32][33] Thus, mitochondrial function might play an important role in cell's radio-sensitivity, and high mitochondrial respiratory capacity of CSCs might be linked with their radio-resistance through DNA repair.…”

Section: Discussionmentioning

confidence: 99%

Metformin preferentially enhances the radio-sensitivity of cancer stem-like cells with highly mitochondrial respiration ability in HMPOS

Deguchi¹,

Hosoya²,

Kim³

et al. 2021

Molecular Therapy - Oncolytics

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Metformin has many anti-cancer effects, alone or in combination with radiation. However, the mechanism underlying its radio-sensitized effect is still unclear, especially for cancer stem-like cells (CSCs). Here, the radio-sensitized effect of metformin was investigated, and its mechanism was revealed in CSCs derived from canine osteosarcoma cell line (HMPOS), a canine osteosarcoma cell line. Spheroid cells (SCs) were used as CSCs-rich cells derived from sphere formation, and SCs were compared with normal adherent culture cells (ACs). The radio-sensitizing effect of metformin using clonogenic assay and tumor growth in mice xenograft model were evaluated, and the mechanism of its radio-sensitization focusing on mitochondrial function was revealed. Metformin significantly enhanced radio-sensitivity of SCs through its inhibition of the mitochondrial function, as shown by decreased oxygen consumption, decreased mitochondrial membrane potential, and decreased ATP production. Additionally, SCs had a higher ability of mitochondrial respiration than ACs, which may have caused difference of their sensitivity of metformin and irradiation. In conclusion, mitochondrial function might play an important role in the sensitivity of metformin and irradiation, and drugs that target mitochondrial respiration, such as metformin, are promising radio-sensitizers to target CSCs.

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Section: Discussionmentioning

confidence: 99%

Metformin preferentially enhances the radio-sensitivity of cancer stem-like cells with highly mitochondrial respiration ability in HMPOS

Deguchi¹,

Hosoya²,

Kim³

et al. 2021

Molecular Therapy - Oncolytics

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“…Coupling x-ray radiation with immunotherapy has shown promising results in preclinical and clinical studies [6,7]. Interestingly, one study has demonstrated that fractionated, but less so single, exposure to x-ray radiation leads to the suppression of glycolytic enzyme expression and decreased lactate production in the tumors [58]. The timing of immunotherapy coupled with conventional radiation therapy needs to be re-evaluated and outcomes might be improved if several fractionations preceded immunotherapy and were applied when lactate levels are at their lowest point.…”

Section: Interplay Between Radiation Therapy and Lactate Production mentioning

confidence: 99%

Cancer Cell Metabolism: Implications for X-ray and Particle Radiation Therapy

Sertorio

Perentesis

Vatner

et al. 2018

International Journal of Particle Therapy

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Advances in radiation delivery technologies and immunotherapy have improved effective cancer treatments and long-term outcomes. Experimental and clinical trials have demonstrated the benefit of a combination of radiation therapy and immunotherapy for tumor eradication. Despite precise radiation dose delivery that is achievable by particle therapy and benefits from reactivating the antitumor immune response, resistance to both therapeutic strategies is frequently observed in patients. Understanding the biological origins of such resistance will create new opportunities for improved cancer treatment. Cancer metabolism and especially a high rate of aerobic glycolysis leading to overproduction and release of lactate is one such biological process favoring tumor progression and treatment resistance. Because of their known protumor effects, aerobic glycolysis and lactate production are potential targets for increased efficacy of radiation alone or in combination with immunotherapy. In the following review, we present an overview of the interplay of cancer cell lactate metabolism with the tumor microenvironment and immune cells. We discuss how a deeper understanding and careful modulation of lactate metabolism and radiation therapy might exploit this interplay for improved therapeutic outcome.

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DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia

et al. 2014

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Glycolysis-related gene induction and ATP reduction during fractionated irradiation

Abstract: Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment.

Cited by 12 publications

References 20 publications

Metformin preferentially enhances the radio-sensitivity of cancer stem-like cells with highly mitochondrial respiration ability in HMPOS

Metformin preferentially enhances the radio-sensitivity of cancer stem-like cells with highly mitochondrial respiration ability in HMPOS

Cancer Cell Metabolism: Implications for X-ray and Particle Radiation Therapy

DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia

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