Resveratrol Inhibits Uveal Melanoma Tumor Growth via Early Mitochondrial Dysfunction

Ginkel, Paul R. van; Darjatmoko, Soesiawati R.; Sareen, Dhruv; Subramanian, Lalita; Bhattacharya, Saswati; Lindstrom, Mary J.; Albert, Daniel M.; Polans, Arthur S.

doi:10.1167/iovs.07-1233

Cited by 57 publications

(62 citation statements)

References 24 publications

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“…Oral resveratrol treatment effectively inhibited tumor growth in two xenograft models of human uveal melanoma in mice. The underlying antitumor mechanisms of resveratrol in these models might have involved activation of the intrinsic mitochondrial pathway leading to release of cytochrome c and Smac/DIABLO, activation of caspase-9 and caspase-3, and tumor cell death by apoptosis (63).…”

Section: Other Systemsmentioning

confidence: 99%

Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical Trials

Bishayee

2009

Cancer Prevention Research

474

325

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Resveratrol (3,4′,5-trihydroxy-trans-stilbene) is a dietary polyphenol derived from grapes, berries, peanuts, and other plant sources. During the last decade, resveratrol has been shown to possess a fascinating spectrum of pharmacologic properties. Multiple biochemical and molecular actions seem to contribute to resveratrol effects against precancerous or cancer cells. Resveratrol affects all three discrete stages of carcinogenesis (initiation, promotion, and progression) by modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis, and metastasis. The anticancer property of resveratrol has been supported by its ability to inhibit proliferation of a wide variety of human tumor cells in vitro. These in vitro data have led to numerous preclinical animal studies to evaluate the potential of this drug for cancer chemoprevention and chemotherapy. This review provides concise, comprehensive data from preclinical in vivo studies in various rodent models of human cancers, highlighting the related mechanisms of action. Bioavailability, pharmacokinetic, and potential toxicity studies of resveratrol in humans and ongoing interventional clinical trials are also presented. The conclusion describes directions for future resveratrol research to establish its activity and utility as a human cancer preventive and therapeutic drug.

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Section: Other Systemsmentioning

confidence: 99%

Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical Trials

Bishayee

2009

Cancer Prevention Research

474

325

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“…Niederkorn and his group [69,70,71,72] published a series of studies using human cell lines in mice (table 4), in which several different human cell lines were successfully transplanted intracamerally in BALB/c (H-2d) athymic mice. Using the human cell lines, not only orthotopic xenografts were established, but also some ectopic xenografts: van Ginkel et al [73] and Triozzi et al [74] successfully placed human cell lines (C918 and MUM2B) subcutaneously into the flanks of athymic mice. Heegaard et al [75] directly implanted UM specimens with the same method and observed a low success rate (13%).…”

Section: Mouse Modelmentioning

confidence: 99%

Animal Eye Models for Uveal Melanoma

Cao

Jager

2015

Ocul Oncol Pathol

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Animal models play an important role in understanding tumor growth and may be used to develop novel therapies against human malignancies. The significance of the results from animal experiments depends on the selection of the proper model. Many attempts have been made to create appropriate animal models for uveal melanoma and its characteristic metastatic behavior. One approach is to use transgenic animal models or to implant tumor cells. A variety of tumor types have been used for this purpose: tumor cells, such as Greene melanoma, murine B16 melanoma, and human uveal melanoma cells, may be implanted in the eyes of hamsters, rats, rabbits, and mice, among others. Various inoculation routes, including into the anterior chamber and posterior compartment, and retro-orbitally, have been applied to obtain tumor growth mimicking ocular uveal melanoma. However, when we choose animal models, we must be conscious of many disadvantages, such as variable tumor growth, or the need for immunosuppression in xenogeneic grafts. In this paper, we will discuss the various eye models.

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“…Moreover, resveratrol has also been shown to stimulate expression of genes for oxidative phosphorylation and mitochondrial biogenesis, which is accompanied with its protective effects against metabolic disease in animal models [66]. Other studies, on the other hand, show that resveratrol and its derivatives can activate the mitochondrial apoptotic pathway in vitro in transformed human cells and in vivo in cancer animal models [67][68][69]. When applied by peritumor injection, resveratrol leads to a decrease of mitochondrial membrane potential in tumor cells [69].…”

Section: Environment Factors That Act On Mitochondriamentioning

confidence: 99%

“…Other studies, on the other hand, show that resveratrol and its derivatives can activate the mitochondrial apoptotic pathway in vitro in transformed human cells and in vivo in cancer animal models [67][68][69]. When applied by peritumor injection, resveratrol leads to a decrease of mitochondrial membrane potential in tumor cells [69]. Other natural polyphenolic compounds, such as quercetin, epigallocatechin-3-gallate (EGCG) and kaempferol, are also found either to restore mitochondrial dysfunctions or to result in tumor cell apoptosis via mitochondria-dependent pathways [70][71][72].…”

Section: Environment Factors That Act On Mitochondriamentioning

confidence: 99%

Picturing Molecular Environmental Health From Mitochondria

Zhou¹

2013

Health Care: Current Reviews

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triphosphate IntroductionHuman diseases are determined by both genetic and environmental risk factors. A recent investigation indicates that environmental factors contribute to about 80% of the 102 diseases and injuries listed by the World Health Organization (WHO) for the year 2002, and account for 24% of the global burden of disease [1]. These data clearly indicate a key role of environmental factors in human health. Modern molecular and cellular studies have revealed a great detail of normal and disease biological processes at the molecular level; however, the molecular mechanisms by which environmental risk factors cause human diseases are still not well understood. An in-depth understanding of these molecular mechanisms is the prerequisite for the design of new strategies of prevention and therapy, and requires intensive investigations in the cutting edge field -Molecular Environmental Health. In this essay, the author uses the organelle mitochondria as an example to connect Molecular Biology and Environmental Health from available literature, to demonstrate the level of clarity of scientific understanding we can achieve by studying environmental health at the molecular and cellular levels. Recent Advances in Mitochondrial BiologyAs an important cellular organelle, mitochondria are known for producing adenosine triphosphate (ATP), buffering calcium and participating apoptosis. Moreover, mitochondria host a variety of metabolic processes, such as the tricarboxylic acid (TCA) cycle, fatty acid beta-oxidation, and synthesis of lipid, steroid, heme and ironsulfur clusters. In the past decades, several significant progresses have been made which have expanded our conventional understanding of the function and regulation of mitochondria.One progress is that mitochondria modulate cellular signal pathways by generating reactive oxygen species (ROS). ROS are oxygencontaining, highly chemically reactive molecules, including superoxide anion, hydroxyl radical and hydrogen peroxide. Mitochondria generate superoxide from oxygen at the site of the mitochondrial electron transport chain as an intrinsic product of oxidative phosphorylation. Traditionally, ROS are considered toxic as high level of ROS causes oxidative damage: protein oxidation, lipid peroxidation and DNA mutation. However, numerous studies have demonstrated that moderate or low levels of ROS are an important cellular signaling transducer in cell proliferation, differentiation and migration [2][3][4][5][6]. In fact, mitochondria-generated superoxide is converted to hydrogen peroxide. Hydrogen peroxide is a signaling messenger that can travel for a distance within the cell to oxidize key protein residues such as cysteines, resulting in change of the conformation or activity of kinases, phosphatases or transcription factors in various cellular signaling pathways. These redox-sensitive signaling pathways, such as the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/Erk), nuclear factor erythroid-derived 2-related factor 2 (Nrf-2), c...

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Resveratrol Inhibits Uveal Melanoma Tumor Growth via Early Mitochondrial Dysfunction

Cited by 57 publications

References 24 publications

Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical Trials

Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical Trials

Animal Eye Models for Uveal Melanoma

Picturing Molecular Environmental Health From Mitochondria

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