Resveratrol induces DNA damage in colon cancer cells by poisoning topoisomerase II and activates the ATM kinase to trigger p53-dependent apoptosis

Demoulin, Benjamin; Hermant, Maryse; Castrogiovanni, Cédric; Staudt, Catherine; Dumont, Patrick

doi:10.1016/j.tiv.2015.04.015

Cited by 75 publications

(49 citation statements)

References 48 publications

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“…The enzyme is mainly located at the nucleus of proliferating cells, and its expression level in proliferating cells is several folds of the one in the resting cells [51–53]. To a certain extent, the expression level of TOP2A reflects the proliferation status of tumors.…”

Section: Discussionmentioning

confidence: 99%

Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan–Meier plotter

et al. 2017

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DNA topoisomerases are essential to modulate DNA topology during various cellular genetic processes. The expression and distinct prognostic value of topoisomerase isoforms in non-small-cell lung cancer (NSCLC) is not well established. In the current study, we have examined the mRNA expression of topoisomerase isoforms by using Oncomine analysis and investigated their prognostic value via the Kaplan–Meier plotter database in NSCLC patients. Our analysis indicated that the expression level of topoisomerases in lung cancer was higher compared with normal tissues. Especially, high expression of two topoisomerase isoforms, TOP2A and TOP3A, was found to be correlated to worse overall survival (OS) in all NSCLC and lung adenocarcinoma (Ade) patients, but not in lung squamous cell carcinoma (SCC) patients. In a contrast, high expression of isoforms TOP1 and TOP2B indicated better OS in all NSCLC and Ade, but not in SCC patients. Meanwhile, high expression of TOP1MT and TOP3B was not correlated with OS in NSCLC patients. Furthermore, we also demonstrated a relationship between topoisomerase isoforms and the clinicopathological features for the NSCLC patients, such as grades, clinical stages, lymph node status, smoking status, gender, chemotherapy and radiotherapy. These results support that TOP2A and TOP3A are associated with worse prognosis in NSCLC patients. In addition, our study also shows that TOP1 and TOP2B contribute to favorable prognosis in NSCLC patients. The exact prognostic significance of TOP1MT and TOP3B need to be further elucidated. Comprehensive evaluation of expression and prognosis of topoisomerase isoforms will be a benefit for the better understanding of heterogeneity and complexity in the molecular biology of NSCLC, paving a way for more accurate prediction of prognosis and discovery of potential drug targets for NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan–Meier plotter

et al. 2017

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“…A study reported that the indirect DNA-damaging effects of resveratrol (30 μM) in colon cancer cells were mainly caused by overproduction of ROS [169]. Another study suggested that the DNA damage induced by resveratrol (25 μM) was due to topoisomerase II poisoning rather than promoting ROS production [170]. Besides, resveratrol (50 μM) suppressed expression of multi-drug resistance protein 1 (MDR1) and drug efflux in drug-resistant colorectal cancer cells [171].…”

Section: Experimental Studiesmentioning

confidence: 99%

Natural Polyphenols for Prevention and Treatment of Cancer

et al. 2016

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There is much epidemiological evidence that a diet rich in fruits and vegetables could lower the risk of certain cancers. The effect has been attributed, in part, to natural polyphenols. Besides, numerous studies have demonstrated that natural polyphenols could be used for the prevention and treatment of cancer. Potential mechanisms included antioxidant, anti-inflammation as well as the modulation of multiple molecular events involved in carcinogenesis. The current review summarized the anticancer efficacy of major polyphenol classes (flavonoids, phenolic acids, lignans and stilbenes) and discussed the potential mechanisms of action, which were based on epidemiological, in vitro, in vivo and clinical studies within the past five years.

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“…However, a low dose enhanced the frequency of γ-H2AX foci after ionising irradiation of prostate epithelial cells [90]. A moderately high concentration applied to colon cancer cells caused γ-H2AX foci, apparently as a result of topoisomerase II poisoning [89]. SBs as well as Fpg-sites were increased in non-cycling cells but decreased in TPA-stimulated, cycling cells [78].…”

Section: Isolated Phytochemicalsmentioning

confidence: 99%

Polyphenols and DNA Damage: A Mixed Blessing

2016

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Polyphenols are a very broad group of chemicals, widely distributed in plant foods, and endowed with antioxidant activity by virtue of their numerous phenol groups. They are widely studied as putative cancer-protective agents, potentially contributing to the cancer preventive properties of fruits and vegetables. We review recent publications relating to human trials, animal experiments and cell culture, grouping them according to whether polyphenols are investigated in whole foods and drinks, in plant extracts, or as individual compounds. A variety of assays are in use to study genetic damage endpoints. Human trials, of which there are rather few, tend to show decreases in endogenous DNA damage and protection against DNA damage induced ex vivo in blood cells. Most animal experiments have investigated the effects of polyphenols (often at high doses) in combination with known DNA-damaging agents, and generally they show protection. High concentrations can themselves induce DNA damage, as demonstrated in numerous cell culture experiments; low concentrations, on the other hand, tend to decrease DNA damage.

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Resveratrol induces DNA damage in colon cancer cells by poisoning topoisomerase II and activates the ATM kinase to trigger p53-dependent apoptosis

Cited by 75 publications

References 48 publications

Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan–Meier plotter

Mining expression and prognosis of topoisomerase isoforms in non-small-cell lung cancer by using Oncomine and Kaplan–Meier plotter

Natural Polyphenols for Prevention and Treatment of Cancer

Polyphenols and DNA Damage: A Mixed Blessing

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