Aging and photo-aging DNA repair phenotype of skin cells—Evidence toward an effect of chronic sun-exposure

Prunier, Chloé; Masson-Genteuil, Gwénaëlle; Ugolin, Nicolas; Sarrazy, Fanny; Sauvaigo, Sylvie

doi:10.1016/j.mrfmmm.2011.05.005

Cited by 14 publications

(12 citation statements)

References 29 publications

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“…On all microarrays each plasmid solution was spotted in duplicate except the control that was deposited 9 times. Excision/synthesis reaction was conducted on the modified plasmid arrays as described in [24] at a final protein concentration of 0.2 mg/mL for all samples. Each extract was tested in duplicate.…”

Section: Methodsmentioning

confidence: 99%

PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitrohepatocellular carcinoma models

et al. 2014

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BackgroundHepatocellular carcinoma is the third cause of cancer related death for which new treatment strategies are needed. Targeting DNA repair pathways to sensitize tumor cells to chemo- or radiotherapy is under investigation for the treatment of several cancers with poly(ADP-ribose) polymerase (PARP) inhibitors showing great potential. The aim of this preclinical study was to evaluate the expression of PARP and PARG genes in a panel of liver cancer cell lines and primary human hepatocytes, their DNA repair capacity and assess the impact on cell survival of PARP inhibitors alone and in combination with radiotherapy.MethodsQuantitative PCR was used to measure PARP-1, -2, -3 and PARG mRNA levels and western blotting for PARP-1 protein expression and ADP-ribose polymer formation after exposure of cells to doxorubicin, a topoisomerase II poison. DNA repair capacity was assessed using an in vitro DNA lesion excision/synthesis assay and the effects on cell killing of the PARP inhibitor ABT-888 alone and in combination with ionizing radiation using clonogenic survival.ResultsAlthough a wide range in expression of the PARPs and PARG was found correlations between PARP-1 and PARP-2 mRNA levels and PARP-1 mRNA and protein levels were noted. However these expression profiles were not predictive of PARP activity in the different cell lines that also showed variability in excision/synthesis repair capacity. 4 of the 7 lines were sensitive to ABT-888 alone and the two lines tested showed enhanced radiosensitivity in the presence of ABT-888.ConclusionsPARP inhibitors combined with radiotherapy show potential as a therapeutic option for hepatocellular carcinoma.

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Section: Methodsmentioning

confidence: 99%

PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitrohepatocellular carcinoma models

et al. 2014

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“…Forskolin, which is a skin-permeable compound, directly activates adenylate cyclase to induce production of cAMP. Our laboratory was among the first to show that topical application of forskolin promoted UV-independent production of eumelanin in an MC1R-defective fair-skinned animal model [53], , resulting in robust UV protection by interfering with epidermal penetration of UV photons [68]. Pharmacologic stimulation of cAMP using forskolin may protect the skin in ways other than through melanin induction.…”

Section: Forskolin Rescues Camp Deficient Signalingmentioning

confidence: 99%

“…Interestingly, cAMP stimulation has also been studied as an activator of hair follicle activity and has been considered as a therapy for age-related hair loss [72, 73]. We and others have been interested in the UV-protective consequences of topical cAMP induction to promote melanin protection from UV-mediated DNA damage [68] and to enhance levels and/or activity of key DNA repair and antioxidant enzymes [74]. Forskolin and other cAMP-promoting agents may also protect the skin against UVB- induced apoptosis [75] and by promoting epidermal thickening which also aids in resisting UV damage [76].…”

Section: Forskolin Rescues Camp Deficient Signalingmentioning

confidence: 99%

“…ROS can inappropriately activate signaling pathways, interfere with genome maintenance and affect apoptosis. Numerous studies have tested the effects of solar radiation and oxidative stress on the skin [29, 83–85], and oxidative stress has been linked to age-related loss of skin elasticity [86–88], defective cellular signaling [68] and photoaging [89, 90]. Because it triggers cellular damage pathways, oxidative stress activates cellular senescence which is thought to directly lead to photoaging [91–94].…”

Section: Oxidative Stress and Agingmentioning

confidence: 99%

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Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

2014

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Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of “realized” solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations.

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“…The modified plasmid microarray has been described elsewhere [33], [36] and is presented as Supporting Information (Methods S1).…”

Section: Methodsmentioning

confidence: 99%

Functional DNA Repair Signature of Cancer Cell Lines Exposed to a Set of Cytotoxic Anticancer Drugs Using a Multiplexed Enzymatic Repair Assay on Biochip

et al. 2012

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The development of resistances to conventional anticancer drugs compromises the efficacy of cancer treatments. In the case of DNA-targeting chemotherapeutic agents, cancer cells may display tolerance to the drug-induced DNA lesions and/or enhanced DNA repair. However, the role of DNA damage response (DDR) and DNA repair in this chemoresistance has yet to be defined. To provide insights in this challenging area, we analyzed the DNA repair signature of 7 cancer cell lines treated by 5 cytotoxic drugs using a recently developed multiplexed functional DNA repair assay. This comprehensive approach considered the complexity and redundancy of the different DNA repair pathways. Data was analyzed using clustering methods and statistical tests. This DNA repair profiling method defined relevant groups based on similarities between different drugs, thus providing information relating to their dominant mechanism of action at the DNA level. Similarly, similarities between different cell lines presumably identified identical functional DDR despite a high level of genetic heterogeneity between cell lines. Our strategy has shed new light on the contribution of specific repair sub-pathways to drug-induced cytotoxicity. Although further molecular characterisations are needed to fully unravel the mechanisms underlying our findings, our approach proved to be very promising to interrogate the complexity of the DNA repair response. Indeed, it could be used to predict the efficacy of a given drug and the chemosensitivity of individual patients, and thus to choose the right treatment for individualised cancer care.

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Aging and photo-aging DNA repair phenotype of skin cells—Evidence toward an effect of chronic sun-exposure

Cited by 14 publications

References 29 publications

PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitrohepatocellular carcinoma models

PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitrohepatocellular carcinoma models

Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

Functional DNA Repair Signature of Cancer Cell Lines Exposed to a Set of Cytotoxic Anticancer Drugs Using a Multiplexed Enzymatic Repair Assay on Biochip

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