Radiation Promptly Alters Cancer Live Cell Metabolic Fluxes: An In Vitro Demonstration

Campos, D; Peeters, Wenny J.M.; Nickel, Kwangok P.; Burkel, Brian; Bussink, Johan; Kimple, Randall J.; Kogel, Albert van der; Eliceiri, Kevin W.; Kissick, M

doi:10.1667/rr14093.1

Cited by 5 publications

(8 citation statements)

References 62 publications

(57 reference statements)

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“…The matched model used here provides an excellent model to study molecular and metabolic pathways associated with radiation resistance in isogenic cell lines. The metabolic changes identified here using endogenous fluorescence are consistent with a recent study by Campos et al 24 . that showed significantly lower mean NADH lifetime in UM-SCC-22B head and neck cancer cells exposed to 10 Gy radiation compared with normal oral keratinocytes, with a lower lifetime indicative of increased glycolysis.…”

Section: Resultssupporting

confidence: 91%

Optical imaging of radiation-induced metabolic changes in radiation-sensitive and resistant cancer cells

et al. 2017

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Abstract. Radiation resistance remains a significant problem for cancer patients, especially due to the time required to definitively determine treatment outcome. For fractionated radiation therapy, nearly 7 to 8 weeks can elapse before a tumor is deemed to be radiation-resistant. We used the optical redox ratio of FAD∕ðFAD þ NADHÞ to identify early metabolic changes in radiation-resistant lung cancer cells. These radiation-resistant human A549 lung cancer cells were developed by exposing the parental A549 cells to repeated doses of radiation (2 Gy). Although there were no significant differences in the optical redox ratio between the parental and resistant cell lines prior to radiation, there was a significant decrease in the optical redox ratio of the radiation-resistant cells 24 h after a single radiation exposure (p ¼ 0.01). This change in the redox ratio was indicative of increased catabolism of glucose in the resistant cells after radiation and was associated with significantly greater protein content of hypoxia-inducible factor 1 (HIF-1α), a key promoter of glycolytic metabolism. Our results demonstrate that the optical redox ratio could provide a rapid method of determining radiation resistance status based on early metabolic changes in cancer cells.

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Section: Resultssupporting

confidence: 91%

Optical imaging of radiation-induced metabolic changes in radiation-sensitive and resistant cancer cells

et al. 2017

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“…The ETC (electron transport chain) uncoupler reactions like addition of CCCP(Carbonyl cyanide m-chlorophenyl hydrazone) or FCCP (Trifluoromethoxy carbonyl cyanide phenyl hydrazone) to cells can be related to this pH sensitivity because mitochondria stay at a higher pH for ETC and will present a drop in the mean fluorescence lifetime. The photo-toxicity or excitation induced stress on the cells and the consequent NADPH response is outside the scope of this study and has been previously discussed in several studies such as mitoflash(60) and irradiation damage(61) studies. However we did not see a strong correlation of the damage using intermittent excitation scheme over time.…”

Section: Resultsmentioning

confidence: 99%

Autofluorescence lifetime imaging of cellular metabolism: Sensitivity toward cell density, pH, intracellular, and intercellular heterogeneity

Chacko

Eliceiri

2018

Cytometry Pt A

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Autofluorescence imaging (AFI) has greatly accelerated in the last decade, way past its origins in detecting endogenous signals in biological tissues to identify differences between samples. There are many endogenous fluorescence sources of contrast but the most robust and widely utilized have been those associated with metabolism. The intrinsically fluorescent metabolic cofactors Nicotinamide adenine dinucleotide (NAD+/NADH) and Flavin adenine dinucleotide (FAD/FADH2) have been utilized in a number of AFI applications including basic research, clinical and pharmaceutical studies. Fluorescence lifetime imaging microscopy (FLIM) has emerged as one of the more powerful AFI tools for NADH and FAD characterization due to its unique ability to non-invasively detect metabolite bound and free states and quantitate cellular redox ratio. However, despite this widespread biological use, many standardization methods are still needed to extend FLIM based AFI into a fully robust research and clinical diagnostic tools. FLIM is sensitive to a wide range of factors in the fluorophore microenvironment and there a number of analysis variables as well. To this end there has been an emphasis on developing imaging standards and ways to make the image acquisition and analysis more consistent. However biological conditions during FLIM based AFI imaging are rarely considered as key sources of FLIM variability. Here we present several experimental factors with supporting data of the cellular microenvironment such as confluency, pH, inter/intra cellular heterogeneity, and choice of cell line that need to be considered for accurate quantitative FLIM based AFI measurement of cellular metabolism.

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“…By quantifying the ratio of free to protein-bound NADH and their respective lifetimes, FLIM can be used to identify the metabolic state of cells and tissue (42, 47–49). A recent study investigated the application of FLIM in radiation research (50). Campos et al first treated human cancer cells and normal oral keratinocytes (NOK) with 10 Gy of radiation and recorded the resultant metabolic changes using FLIM.…”

Section: Optical Microscopymentioning

confidence: 99%

Optical Imaging Approaches to Investigating Radiation Resistance

Dadgar

Rajaram

2019

Front. Oncol.

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Radiation therapy is frequently the first line of treatment for over 50% of cancer patients. While great advances have been made in improving treatment response rates and reducing damage to normal tissue, radiation resistance remains a persistent clinical problem. While hypoxia or a lack of tumor oxygenation has long been considered a key factor in causing treatment failure, recent evidence points to metabolic reprogramming under well-oxygenated conditions as a potential route to promoting radiation resistance. In this review, we present recent studies from our lab and others that use high-resolution optical imaging as well as clinical translational optical spectroscopy to shine light on the biological basis of radiation resistance. Two-photon microscopy of endogenous cellular metabolism has identified key changes in both mitochondrial structure and function that are specific to radiation-resistant cells and help promote cell survival in response to radiation. Optical spectroscopic approaches, such as diffuse reflectance and Raman spectroscopy have demonstrated functional and molecular differences between radiation-resistant and sensitive tumors in response to radiation. These studies have uncovered key changes in metabolic pathways and present a viable route to clinical translation of optical technologies to determine radiation resistance at a very early stage in the clinic.

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Radiation Promptly Alters Cancer Live Cell Metabolic Fluxes: An In Vitro Demonstration

Cited by 5 publications

References 62 publications

Optical imaging of radiation-induced metabolic changes in radiation-sensitive and resistant cancer cells

Optical imaging of radiation-induced metabolic changes in radiation-sensitive and resistant cancer cells

Autofluorescence lifetime imaging of cellular metabolism: Sensitivity toward cell density, pH, intracellular, and intercellular heterogeneity

Optical Imaging Approaches to Investigating Radiation Resistance

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