Resveratrol: A review of preclinical studies for human cancer prevention

Athar, Mohammad; Back, Jung Ho; Tang, Xiuwei; Kim, Kwang Ho; Kopelovich, Levy; Bickers, David R.; Kim, Arianna L.

doi:10.1016/j.taap.2006.12.025

Cited by 648 publications

(464 citation statements)

References 107 publications

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“…In animal models, it is neuroprotective after traumatic brain injury and also protects against diabetic oxidative damage by ameliorating oxidative-stress markers in the brain [27,28]. Meanwhile, this compound possesses cancer suppression activity on a variety of human and rodent cancers [29][30][31] including the primary brain malignancies [18,22,32]. Moreover, the effective anti-cancer dose of resveratrol exerts few harmful effects on primary cultures of rat glial cells and neurons [18].…”

Section: Discussionmentioning

confidence: 99%

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Shu

Wang

et al. 2015

Neurotherapeutics

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Resveratrol possesses anti-tumor activities against central nervous system (CNS) tumors in vitro but has not yet been used clinically due to its low bioavailability, particularly in the CNS. This study thus aimed to elucidate brain bioavailability of trans-resveratrol by monitoring brain concentrations and dwell times following administration of resveratrol through intragastric, intraperitoneal, external carotid artery/ ECA and intrathecal routes. In parallel, we evaluated the biological responses of rat RG2 glioblastoma cells as well as RG2-formed rat intracranial glioblastomas treated with resveratrol via intrathecal administration. The results revealed that resveratrol was detected in rat brains except when administered systemically. Intrathecal administration of reseveratrol led to abundant apoptotic foci and increased staining of the autophagy proteins, LC-3 and Beclin-1 and shrinkage of the intracranial tumors. In conclusion, the BBB penetrability of resveratrol is remarkably increased by intracthecal administration. Regular short-term resveratrol treatments suppress growth and enhance autophagic and apoptotic activities of rat RG2 glioblastoma cells in vitro and in vivo. Therefore, intrathecal administration of resveratrol could be an optimal intervention approach in the adjuvant management of brain malignancies.

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Section: Discussionmentioning

confidence: 99%

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Shu

Wang

et al. 2015

Neurotherapeutics

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“…Resveratrol is a natural product induced in plants after a variety of stresses and shows potential cancer chemoprotective properties (Athar et al, 2007). Activation of SIRT1 may be a useful chemopreventative agent in age-related cancers, such as prostate cancer in which deacetylation of the AR inactivates its ability to transform prostate cells (Fu et al, 2006).…”

Section: Therapeutic Potential Of Sirtuin Regulationmentioning

confidence: 99%

Sirtuins: critical regulators at the crossroads between cancer and aging

2007

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Sirtuins (SIRTs 1À7), or class III histone deacetylases (HDACs), are protein deacetylases/ADP ribosyltransferases that target a wide range of cellular proteins in the nucleus, cytoplasm, and mitochondria for post-translational modification by acetylation (SIRT1, -2, -3 and -5) or ADP ribosylation (SIRT4 and -6). The orthologs of sirtuins in lower organisms play a critical role in regulating lifespan. As cancer is a disease of aging, we discuss the growing implications of the sirtuins in protecting against cancer development. Sirtuins regulate the cellular responses to stress and ensure that damaged DNA is not propagated and that mutations do not accumulate. SIRT1 also promotes replicative senescence under conditions of chronic stress. By participating in the stress response to genomic insults, sirtuins are thought to protect against cancer, but they are also emerging as direct participants in the growth of some cancers. Here, we review the growing implications of sirtuins both in cancer prevention and as specific and novel cancer therapeutic targets.

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“…Resveratrol (trans-3,5,4Ј-trihydroxy-trans-stilbene) is a naturally occurring compound that has been shown to prevent some forms of cancer (12)(13)(14) and other inflammatory diseases (15,16); however, the mechanism of action remains to be elucidated. Notably, resveratrol has been shown to inhibit the peroxidase activity of MPO (17); however, no studies have been published regarding its ability to scavenge HOCl.…”

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confidence: 99%

Myeloperoxidase-induced Genomic DNA-centered Radicals

Gomez-Mejiba

Zhai

Giménez

et al. 2010

Journal of Biological Chemistry

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Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote carcinogenesis. MPO produces hypochlorous acid (HOCl) that oxidizes the genomic DNA in inflammatory cells as well as in surrounding epithelial cells. DNA-centered radicals are early intermediates formed during DNA oxidation. Once formed, DNA-centered radicals decay by mechanisms that are not completely understood, producing a number of oxidation products that are studied as markers of DNA oxidation. In this study we employed the 5,5-dimethyl-1-pyrroline N-oxide-based immuno-spin trapping technique to investigate the MPO-triggered formation of DNA-centered radicals in inflammatory and epithelial cells and to test whether resveratrol blocks HOCl-induced DNA-centered radical formation in these cells. We found that HOCl added exogenously or generated intracellularly by MPO that has been taken up by the cell or by MPO newly synthesized produces DNA-centered radicals inside cells. We also found that resveratrol passed across cell membranes and scavenged HOCl before it reacted with the genomic DNA, thus blocking DNA-centered radical formation. Taken together our results indicate that the formation of DNA-centered radicals by intracellular MPO may be a useful point of therapeutic intervention in inflammation-induced carcinogenesis.Activation of neutrophils can initiate chemical mutagenesis and carcinogenesis by producing oxidative damage to the genome in the inflammatory environment (1-3). Myeloperoxidase (MPO, 4 donor hydrogen peroxide, oxidoreductase, EC 1.11.1.7), is a hemeprotein found in the azurophilic granules of neutrophils (4 -6). MPO uses H 2 O 2 to oxidize chloride ions, converting them into the powerful oxidant hypochlorous acid (HOCl/OCl Ϫ , pK a ϭ 7.46) (5). Although other mammalian peroxidases can oxidize a number of halides and pseudohalides to hypohalous and pseudohypohalous acids, MPO is the only mammalian enzyme that produces HOCl under physiological conditions (5). In sites of inflammation, H 2 O 2 used in the MPOcatalyzed oxidation of chloride is produced by dismutation of superoxide radical anion (O 2 . ). It is noteworthy that DNA is negatively charged and MPO is a cationic protein (5), which suggests that they can bind each other by electrostatic interactions. MPO is known to be taken up by cells surrounding an inflammatory site (7). It might be anticipated that this would make them highly vulnerable to DNA damage induced by H 2 O 2 . DNA-chloramines, which are less reactive than HOCl, are produced when HOCl reacts with DNA at its heterocyclic (ring) amino groups of guanosine and thymine groups and with exocyclic amino groups of guanosine, adenosine, and cytidine (8). Once formed, DNA-chloramines appear to undergo both one-and two-electron decay to produce DNA nitrogen-centered radicals, a process that is catalyzed by reduced metals and is promoted by UV irradiation and high temperatures (8 -9). Importantly, nitrogen-and carboncentered radicals can be trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to form radic...

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Resveratrol: A review of preclinical studies for human cancer prevention

Cited by 648 publications

References 107 publications

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Sirtuins: critical regulators at the crossroads between cancer and aging

Myeloperoxidase-induced Genomic DNA-centered Radicals

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