Resveratrol enhances the suppressive effects of arsenic trioxide on primitive leukemic progenitors

Wu, Edward J.; Goussetis, Dennis J.; Beauchamp, Elspeth M.; Kościuczuk, Ewa M.; Altman, Jessica K.; Eklund, Elizabeth A.; Platanias, Leonidas C.

doi:10.4161/cbt.27824

Cited by 14 publications

(7 citation statements)

References 33 publications

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“…Current evidence suggests that resveratrol enhances the antileukemic properties of As 2 O 3 [24] . Thus we investigated whether the combination of As 2 O 3 and resveratrol has stronger antitumor effect in various cancer cell lines compared with As 2 O 3 or resveratrol alone.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol and Arsenic Trioxide Act Synergistically to Kill Tumor Cells In Vitro and In Vivo

et al. 2014

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Background and AimsArsenic trioxide (As2O3), which used as an effective agent in the treatment of leukaemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden heart death have been implicated in the cardiotoxicity of As2O3. The present study was designed to explore whether the combination of As2O3 and resveratrol could generate a more powerful anti-cancer effect both in vitro and in vivo.Materials and MethodsMTT assay was performed to assess the proliferation of Hela, MCF-7 and NB4 cells. Isobolographic analysis was used to evaluate combination index values from cell viability data. The apoptosis and the cellular reactive oxygen species (ROS) level were assessed by fluorescent microscopy and flow cytometry separately in vitro. The effect of As2O3, alone and in combination with resveratrol on Hela tumor growth in an orthotopic nude mouse model was also investigated. The tumor volume and the immunohistochemical analysis of CD31, CD34 and VEGF were determined.ResultsResveratrol dramatically enhanced the anti-cancer effect induced by As2O3 in vitro. In addition, isobolographic analysis further demonstrated that As2O3 and resveratrol generated a synergistic action. More apoptosis and ROS generation were observed in the combination treatment group. Similar synergistic effects were found in nude mice in vivo. The combination of As2O3 and resveratrol dramatically suppressed both tumor growth and angiogenesis in nude mice.ConclusionsCombining As2O3 with resveratrol would be a novel strategy to treat cancer in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Resveratrol and Arsenic Trioxide Act Synergistically to Kill Tumor Cells In Vitro and In Vivo

et al. 2014

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“…Formation of diethylstilbestrol–DNA adducts, as a side effect of hormone treatment, is reduced by concomitant treatment with Resv [ 18 ] and EGFR inhibition by gefitinib [ 19 ], and the apoptosis-inducing effect of arsenic trioxide is potentiated by Resv [ 20 ] ( Table S1 ). Further, flutamide is used as an anti-androgen in hormone treatment of prostate cancer, and the activity of flutamide was synergized by simultaneous treatment with Resv [ 21 ].…”

Section: The Combinatory Effect—a Boosted Effect?mentioning

confidence: 99%

Challenges in Analyzing the Biological Effects of Resveratrol

Erdoğan

Vang

2016

Nutrients

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The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biological effects. Extrapolating the biological effects of dietary compounds from in vitro and in vivo animal experiments to humans may lead to over- or under-estimation of the effect and role of these compounds. The present paper will discuss a few of these challenges and suggest directions for future research. Questions we address include: (1) Is the combinatorial effect of resveratrol and other compounds real? (2) What are the real and relevant doses of resveratrol after administration? and (3) Is it possible to estimate the preventive effect of resveratrol by clinical trials using standard experimental designs? The examples concerning resveratrol taken from the scientific literature are mainly from 2010 and later. The challenges pointed out in this review are similar to most naturally occurring bioactive compounds.

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“…Many autophagy-inducing natural products, including berberine, curcumin, and resveratrol, could enhance the therapeutic effect of other agents, and this synergistic effect is correlated with induction of autophagy. Peng et al found that berberine could enhance tumor-killing action of irradiation by inducing autophagic cell death [ 120 ]; curcumin was found to sensitize cancer cells towards treatment of 7-deoxypancratistatin, a novel chemotherapeutic agent [ 121 ]; resveratrol-initiated autophagy enhances the cytotoxicity of arsenic oxide on primitive leukemic progenitors, indicating a positive role of autophagy induction in the combination treatment of arsenic oxide and resveratrol against leukemia [ 122 ]. The enhancing action of natural products-induced autophagy could also be observed in some herbal extracts including Koelreuteria henryi Dummer and Emblica officinalis [ 123 , 124 ].…”

Section: Direction Of Future Studymentioning

confidence: 99%

Elaborating the Role of Natural Products-Induced Autophagy in Cancer Treatment: Achievements and Artifacts in the State of the Art

Wang

Feng

2015

BioMed Research International

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Autophagy is a homeostatic process that is highly conserved across different types of mammalian cells. Autophagy is able to relieve tumor cell from nutrient and oxidative stress during the rapid expansion of cancer. Excessive and sustained autophagy may lead to cell death and tumor shrinkage. It was shown in literature that many anticancer natural compounds and extracts could initiate autophagy in tumor cells. As summarized in this review, the tumor suppressive action of natural products-induced autophagy may lead to cell senescence, provoke apoptosis-independent cell death, and complement apoptotic cell death by robust or target-specific mechanisms. In some cases, natural products-induced autophagy could protect tumor cells from apoptotic death. Technical variations in detecting autophagy affect data quality, and study focus should be made on elaborating the role of autophagy in deciding cell fate. In vivo study monitoring of autophagy in cancer treatment is expected to be the future direction. The clinical-relevant action of autophagy-inducing natural products should be highlighted in future study. As natural products are an important resource in discovery of lead compound of anticancer drug, study on the role of autophagy in tumor suppressive effect of natural products continues to be necessary and emerging.

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Resveratrol enhances the suppressive effects of arsenic trioxide on primitive leukemic progenitors

Cited by 14 publications

References 33 publications

Resveratrol and Arsenic Trioxide Act Synergistically to Kill Tumor Cells In Vitro and In Vivo

Resveratrol and Arsenic Trioxide Act Synergistically to Kill Tumor Cells In Vitro and In Vivo

Challenges in Analyzing the Biological Effects of Resveratrol

Elaborating the Role of Natural Products-Induced Autophagy in Cancer Treatment: Achievements and Artifacts in the State of the Art

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