Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction

Pearson, Kevin J.; Lewis, Kaitlyn N.; Price, Nathan L.; Chang, Joy; Perez, Evelyn; Cascajo, Maria V; Tamashiro, Kellie L.K.; Poosala, Suresh; Csiszár, Anna; Ungvári, Zoltán; Kensler, Thomas W.; Yamamoto, Masayuki; Egan, Josephine M.; Longo, Dan L.; Ingram, Donald K.; Navas, Plácido; Cabo, Rafael de

doi:10.1073/pnas.0712162105

Cited by 214 publications

(164 citation statements)

References 42 publications

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“…CR was not effective against chemically induced tumorigenesis in the NFE2L2 knockout (KO) mice. AL NFE2L2 KO and CR NFE2L2 KO mice reached total tumor incidence at the age of 30 weeks, while 40% CR wt mice did not show any papillomas until 42 weeks of treatment (73). These data suggest that the anticarcinogenic effect of CR solely depends on the activity of NFE2L2 due to the lack of activation of the antioxidant defenses.…”

Section: Martin-montalvo and De Cabomentioning

confidence: 56%

Mitochondrial Metabolic Reprogramming Induced by Calorie Restriction

Martín-Montalvo

Cabo

2013

Antioxidants & Redox Signaling

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Significance: Calorie restriction (CR) is a known intervention that delays most aging processes. Most of the beneficial effects of CR are mediated by improved maintenance of mitochondrial performance in aged individuals. The control of mitochondrial biogenesis, apoptosis, and protein turnover is required for healthy aging. CR is able to induce molecular mechanisms that preserve oxidative capacity and decrease oxidative damage. Recent Advances and Critical Issues: Published data indicate that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1a) is activated in old animals under CR conditions compared to ad libitum counterparts, enhancing mitochondrial biogenesis. Molecular regulation of PGC-1a has recently attracted significant research interest. We discuss the master regulators of energy metabolism such as AMP-activated protein kinase and sirtuin 1 among others that have been demonstrated to activate mitochondrial biogenesis through increased PGC-1a activity at transcriptional and post-translational levels. Additionally, we describe the latest findings that explain how CR promotes mitochondrial efficiency and decreases mitochondrial-derived oxidative damage. Future Directions: Understanding the beneficial mitochondrial changes conferred by CR will aid design of therapies for age-related diseases and help slow the aging process. Given the difficulty for humans to adhere to CR, we also explore new molecules that have been proposed during the last years to mimic the CR phenotype and their potential as future therapeutics. Antioxid. Redox Signal. 19, 310-320.

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Section: Martin-montalvo and De Cabomentioning

confidence: 56%

Mitochondrial Metabolic Reprogramming Induced by Calorie Restriction

Martín-Montalvo

Cabo

2013

Antioxidants & Redox Signaling

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“…Pearson et al [13] found one of the possible pathways that led from caloric restriction to anti cancer activity: Nrf2.…”

Section: Addressing Tumor Heterogeneitymentioning

confidence: 99%

“…Also certain compounds like sulforaphane and resveratrol can mimic the translational modifications found under caloric restriction [13][14].…”

Section: Addressing Tumor Heterogeneitymentioning

confidence: 99%

Tumor heterogeneity: An overlooked issue in cancer therapeutics

Koltai¹

2017

Integr Cancer Sci Therap.

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“…Interestingly, caloric restriction mimetic agents and caloric restriction activate Nrf2, 57 along with the activity of enzymes of the plasma membrane redox system, 57 so that Nrf2 has been implicated in the cancer protection induced by caloric restriction. 58 Furthermore, one of the consequences of Nrf2 activation in caloric restriction is to restrain vascular aging by reinforcing the antioxidant defenses of endothelial cells. 59 A number of experimental studies show that 4HPR, resveratrol, curcumin, xanthohumol, the isothiocyanate PEITC and CDDO triterpenoids can produce a dose-dependent prooxidant state inside tumor cells.…”

Section: Caloric Restriction and Angiopreventionmentioning

confidence: 99%

Metabolic regulation and redox activity as mechanisms for angioprevention by dietary phytochemicals

Tosetti

Noonan

Albini

2009

Intl Journal of Cancer

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The existence of active principles in numerous foods and beverages has been recognized by traditional medicines worldwide after centuries of empirical trial. Epidemiological studies support the concepts linking diet to survival, particularly in the incidence rates of specific cancers. Molecular studies have provided evidence that a wide range of food-derived phytochemicals and other dietassociated compounds or their synthetic derivatives represent a cornucopia of potential new compounds for prevention and treatment of chronic or acute diseases. Many have entered clinical practice or are under clinical testing. A remarkable property shared by several phytochemicals is the capacity to restrain inflammation and angiogenesis, two complex physiologic processes kept under control by strict rules, which can backfire in cancer and in pathologic conditions such as metabolic, cardiovascular and neurological disorders. We termed this concept ''angioprevention''. Here, we discuss recent findings on the metabolic effects of several phytochemicals with anticancer properties. The different molecular targets shared by these compounds seem to converge on crosstalking signaling networks involved in controlling energy metabolism through a redox-regulated code. The redox imbalance produced in the tissue microenvironment elicits an adaptive response that seems to provide cytoprotective effects potentially beneficial in cardiovascular and neurological disorders or energy balancing effects in metabolic disorders. However, in transformed and overt tumor cells, this redox imbalance favors cell death while curbing tumor inflammation and angiogenesis, thus engaging an overall antitumor response. These concepts provide a broader framework for pharmacological application of phytochemical-derived drugs against cancer. ' UICCKey words: chemoprevention; cancer; angiogenesis; inflammation; redox; angioprevention; oxidative stress; aging; longevity The term ''chemoprevention'' was proposed by Sporn 1 more than 30 years ago to describe pharmacologic or dietary interventions that would interfere with the carcinogenic process, resulting in decreased cancer risk, a ''descendent'' of the cancer chemoprophylaxis concept. The scope of dietary cancer prophylaxis is not only to avoid cancer but also to transform overt cancer into a chronic disease. After evidence from empirical traditional medicine and decades of preclinical testing, we are now witnessing clinical application of several dietary phytochemicals in experimental trials of chemoprevention and intervention for solid tumors and hematologic malignancies. About 30 NIH-registered clinical trials are ongoing to test the efficacy of curcumin, a principle contained in turmeric, the yellow component of curry from the rhizome of Curcuma longa L., used as an antiinflammatory agent for centuries in traditional Asian medicine. Ten clinical trials are active for the polyphenol found in red grapes, resveratrol, and nearly 30 studies are using green tea extracts or the active flavonoid component epigalloca...

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Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction

Cited by 214 publications

References 42 publications

Mitochondrial Metabolic Reprogramming Induced by Calorie Restriction

Mitochondrial Metabolic Reprogramming Induced by Calorie Restriction

Tumor heterogeneity: An overlooked issue in cancer therapeutics

Metabolic regulation and redox activity as mechanisms for angioprevention by dietary phytochemicals

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