Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for Radiosensitization of Human Cancer Cells

Sanli, Toran; Rashid, Ayesha; Liu, Caiqiong; Harding, Shane M.; Bristow, Robert G.; Cutz, Jean Claude; Singh, Gurmit; Wright, James Homer; Tsakiridis, Theodoros

doi:10.1016/j.ijrobp.2010.03.005

Cited by 181 publications

(228 citation statements)

References 31 publications

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“…To the best of our knowledge, an investigation of the radiosensitizing potential of the combination of metformin and X-ray radiation has not yet been reported, although metformin has recently been reported to modify γ-ray response in lung cancer (25). Based on our results, metformin significantly enhanced the radiation response, as the number of colonies of hepatoma cells in the combined treatment group was significantly lower than that of each individual treatment group, implying that metformin may function as a potential radiation sensitizer for cancer radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Enhanced cytotoxic effect of low doses of metformin combined with ionizing radiation on hepatoma cells via ATP deprivation and inhibition of DNA repair

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Enhanced cytotoxic effect of low doses of metformin combined with ionizing radiation on hepatoma cells via ATP deprivation and inhibition of DNA repair

et al. 2012

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“…A previous study reported that ionic radiation increased AMPK protein levels in lung cancer and breast cancer cells (12). In the present study, the importance of AMPK in radiation resistance in colon cancer cells was assessed and highlighted the clinical relevance by inhibition of AMPK, suggesting a therapeutic role of AMPK inhibitor for overcoming radiation resistance.…”

Section: Discussionmentioning

confidence: 52%

Re-sensitization of radiation resistant colorectal cancer cells to radiation through inhibition of AMPK pathway

et al. 2016

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Abstract. Radiotherapy (RT) is commonly used to treat multi-tumors to attenuate the risk of recurrence. Despite impressive initial clinical responses, a large proportion of patients experience resistance to RT. Therefore, identification of functionally relevant biomarkers would be beneficial for radioresistant patients. Adenosine monophosphate-activated kinase (AMPK) is recognized as a mediator of tumor suppressor gene function. In the present study, radio-sensitive and -resistant colon cancer patient samples were compared and the AMPK pathway was observed to be highly activated in radioresistant patients. In addition, the protein and mRNA levels of AMPK were upregulated in radioresistant colon cancer cells in comparison to radiosensitive colon cancer cells. The present study provides evidence that activation of AMPK by metformin contributes to radioresistance. Inhibition of AMPK by either small interfering RNA or Compound C, which is a specific inhibitor of AMPK, re-sensitized radiation resistant cells. The data presented indicates a synergistic effect on radiation resistant cancer cells by the combination of Compound C and radiation. In summary, the present study proposes that inhibition of the AMPK pathway is a potential strategy for reversing radiation resistance and may contribute to the development of therapeutic anticancer drugs.

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“…Also, patients with A-T have been shown to have noticeable insulin resistance and increased risk of diabetes [90,91]. Further, previous reports indicate that inhibition or activation of ATM changes AMPK activation [92][93][94]. Not one of the other genes have been identified to be associated with diabetes or insulin action at the locus.…”

Section: Resultsmentioning

confidence: 99%

Integration and Weighing of Omics Data for Obesity

Brettfeld¹,

Maver²

2016

J Diabetes Metab

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Objective: OMICs research has become of great interest over the last years and enabled the research community to acquisition an increasing amount of data. In a prior study by our group, we have employed a novel positional integrative approach. For this second study we utilized the same integration method but weighed each individual data source trying to verify our already found regions and/or identify new gene regions of interest for obesity. Method:In contrast to previous methodologies employed for integration of heterogeneous OMIC data, we based the integration on genomic positions of alterations in human disease and employed an additional weighing step. A data search for various types of studies on Obesity (genome-wide association, meta-analysis, transcriptomic, proteomic studies and epigenetic studies) was conducted to establish the initial data set. For this study, five different weighing settings were used, to individually double the input of genomic data, transcriptomic data, proteomic data, microRNA data and epigenetic data in comparison to all the other data sources. Results and discussion:The analysis identified ten gene regions (ATP5O, ALK7, GAPDH, IFFO1, NCAPD2, DDX50, MAOB, ATM, STOX1 and PRRC2A). ATP5O, ALK7 and GADPH were also identified in our prior study as the highest scoring gene regions and prove to be consistent in our data set. Even though, the ten high ranked and discussed genes could not be directly linked to obesity nine of them are associated with Type 2 Diabetes or a neurodegenerative disease. Both disorders show a higher prevalence in obese individuals compared to lean. Conclusion:In this study, we applied a new method of positional integrational analysis of different OMIC-layers and an additional validation step through weighing. our study provides a basis for further research to elucidate underlying mechanisms of these associations and identify new targets for preventive and therapeutic interventions.

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Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for Radiosensitization of Human Cancer Cells

Cited by 181 publications

References 31 publications

Enhanced cytotoxic effect of low doses of metformin combined with ionizing radiation on hepatoma cells via ATP deprivation and inhibition of DNA repair

Enhanced cytotoxic effect of low doses of metformin combined with ionizing radiation on hepatoma cells via ATP deprivation and inhibition of DNA repair

Re-sensitization of radiation resistant colorectal cancer cells to radiation through inhibition of AMPK pathway

Integration and Weighing of Omics Data for Obesity

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