Resveratrol chemosensitizes breast cancer cells to melphalan by cell cycle arrest

Casanova, Fabiana Alves; Quarti, Julia; Costa, David G.; Ramos, Caroline Araújo; Silva, Jerson L.; Fialho, Eliane

doi:10.1002/jcb.24134

Cited by 70 publications

(58 citation statements)

References 34 publications

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“…18 The treatment with resveratrol increased the levels of activated checkpoint kinase 2 expression (p-Chk2), which showed a decrease of cyclin A expression. 19 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form [Thr(160)-phosphorylated CDK2] was decreased by treatment with resveratrol. 19 The activity of CDK7, the kinase that phosphorylates CDK2 at Thr(160), was inhibited by resveratrol.…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…19 While the levels of cyclin dependent kinase 2 (CDK2) remained unchanged by treatments, its active form [Thr(160)-phosphorylated CDK2] was decreased by treatment with resveratrol. 19 The activity of CDK7, the kinase that phosphorylates CDK2 at Thr(160), was inhibited by resveratrol. 19 Although the efficacy on the apoptosis process has been documented, the bioefficacy is yet a matter of debate.…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…19 The activity of CDK7, the kinase that phosphorylates CDK2 at Thr(160), was inhibited by resveratrol. 19 Although the efficacy on the apoptosis process has been documented, the bioefficacy is yet a matter of debate. For this reason, resveratrol was compared with its derivatives, triacetyl-resveratrol (trans-3,5,4 0 -triacetylstilbene) and trimethoxy-resveratrol (trans-3,5,4 0 -trimethoxystilbene) in both estrogen receptor-a (ERa)-positive and ERa-negative breast cancer cells.…”

Section: In Vitro Studiesmentioning

confidence: 99%

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Use of Grape Polyphenols Against Carcinogenesis: Putative Molecular Mechanisms of Action Using In Vitro and In Vivo Test Systems

Gollucke

Aguiar²,

Barbisan³

et al. 2013

Journal of Medicinal Food

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Polyphenols are present in foods and beverages and are related to sensorial qualities such as color, bitterness, and astringency, which are relevant in wine, tea, grape juice, and other products. These compounds occur naturally in forms varying from simple phenolic acids to complex polymerized tannins. Thus, it is reasonable to expect that grape-derived products elaborated in the presence of skins and seeds, such as wine and grape juice, are natural sources of flavonoids in the diet. Carcinogenesis is a multistep process that is characterized by genetic, epigenetic, and phenotypic changes. With increasing knowledge of these mechanisms, and the conclusion that most cases of cancer are preventable, efforts have focused on identifying the agents with potential anticancer properties. The use of grape polyphenols against the carcinogenesis process seems to be a suitable alternative for either prevention and/or therapeutic purposes. The aim of this article is to show the molecular data generated from the use of grape polyphenols against carcinogenesis using in vivo and in vitro test systems.

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Section: In Vitro Studiesmentioning

confidence: 99%

Section: In Vitro Studiesmentioning

confidence: 99%

Section: In Vitro Studiesmentioning

confidence: 99%

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Use of Grape Polyphenols Against Carcinogenesis: Putative Molecular Mechanisms of Action Using In Vitro and In Vivo Test Systems

Gollucke

Aguiar²,

Barbisan³

et al. 2013

Journal of Medicinal Food

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“…MDA-MB-231, one of the breast cancer cell lines commonly used in cancer research, normally has poor prognosis [2]. It is reported that, the combination treatment of phenolic compounds from plant such as resveratrol together with melphalan could inhibit MDA-MB-231 cells more efficiently [3]. Hence, natural phenolics had a great potential to be the anti-cancer agents.…”

Section: Introductionmentioning

confidence: 99%

The comparative study among different fractions of muscadine grape ‘Noble’ pomace extracts regarding anti-oxidative activities, cell cycle arrest and apoptosis in breast cancer

Luo

Song

et al. 2017

Food & Nutrition Research

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As a by-product of wine making, pomace contains rich amounts of phenolic compounds that can be potentially utilized as raw materials to make beneficial products especially for the anti-cancer agents including the breast cancer. Muscadinia rotundifolia ‘Noble’ is a wine-making grape cultivar, and to better use ‘Noble’ pomace, the most effective phenolic fractions in cancer inhibition must be identified. In this study, anti-oxidative activities of three separated fractions of ‘Noble’ pomace (F1, F2 and F3) were compared in 2,2-diphenyl-1-picrylhydrazyl and 2,2ʹ-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging (DPPH and ABTS) assays as well as the ferric-reducing antioxidant power (FRAP) assay. The ability of different fractions to induce cell cycle arrest and apoptosis in MDA-MB-231 breast cancer cells was also evaluated by flow cytometry and Western blot analysis. Fraction F3, which contained a mixture of anthocyanidins and ellagic acids, exhibited the strongest anti-oxidative activity, as determined at both low and high concentrations in the DPPH and FRAP assays. F3 also demonstrated the greatest ability to induce apoptosis via caspase activation and cell cycle arrest by downregulating cyclin A and upregulating p21. F3 was thus the most effective bioactive fraction among those prepared from muscadine grape ‘Noble’ pomace.

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“…A previous study suggested that resveratrol can chemosensitize breast cancer cells to chemotherapeutics drugs [16]. Recently, Sprouse et al…”

mentioning

confidence: 98%

Resveratrol Enhances Etoposide‐Induced Cytotoxicity through Down‐Regulating ERK1/2 and AKT‐Mediated X‐ray Repair Cross‐Complement Group 1 (XRCC1) Protein Expression in Human Non‐Small‐Cell Lung Cancer Cells

Syu

Chen

et al. 2015

Basic Clin Pharma Tox

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Etoposide (VP-16), a topoisomerase II inhibitor, is an effective anti-cancer drug used for the treatment of non-smallcell lung cancer (NSCLC). Resveratrol is a naturally occurring polyphenolic compound that has been proved to have anti-cancer activity. XRCC1 is an important scaffold protein involved in base excision repair that is regulated by ERK1/2 and AKT signals and plays an important role in the development of lung cancer. However, the role of ERK1/2 and AKT-mediated XRCC1 expression in etoposide treatment alone or combined with resveratrol-induced cytotoxicity in NSCLC cells has not been identified. In this study, etoposide treatment increased XRCC1 mRNA and protein expression through AKT and ERK1/2 activation in two NSCLC cells, H1703 and H1975. Knockdown of XRCC1 in NSCLC cells by transfection of XRCC1 siRNA or inactivation of ERK1/2 and AKT resulted in enhancing cytotoxicity and cell growth inhibition induced by etoposide. Resveratrol inhibited the expression of XRCC1 and enhanced the etoposide-induced cell death and anti-proliferation effect in NSCLC cells. Furthermore, transfection with constitutive active MKK1 or AKT vectors could rescue the XRCC1 protein level and also the cell survival suppressed by co-treatment with etoposide and resveratrol. These findings suggested that down-regulation of XRCC1 expression by resveratrol can enhance the chemosensitivity of etoposide in NSCLC cells.Lung cancer, the leading cause of cancer death in the world, is classified as non-small-cell lung cancer (NSCLC) and small-cell lung cancer [1]. NSCLC accounts for 85% of lung cancer cases, and despite aggressive radio-and/or chemotherapy, fewer than 20% of patients reach a 5-year survival. This poor treatment outcome is due to the primary or acquired drug resistance of NSCLC cells to present cytotoxic therapeutic agents [2,3].Etoposide is an epipodophyllotoxin employed in the therapy of a wide spectrum of cancers [4][5][6]. In vitro studies have shown that etoposide increases topoisomerase II-mediated DNA breakage primarily by inhibiting the ability of the enzyme to religate cleaved nucleic acid molecules [7]. XRCC1 (X-ray repair cross-complementing group 1) is a key mediator of base excision repair (BER). Deficiency of XRCC1 in mice results in embryonic lethality [8,9]. XRCC1 interacts with enzymatic factors such as polyadenosine diphosphate (ADP)-ribose polymerase, DNA ligase III and DNA polymerase b to facilitate efficient repair of DNA single-strand breaks (SSBs) [10]. Down-regulation of XRCC1 expression in human breast cancer cell lines resulted in decreased SSB repair capacity and hypersensitivity to methyl methane sulphonate (MMS) [11]. A previous study has shown that the PI3K-AKT pathway regulates the basal expression of XRCC1 in non-irradiated cells, and MKK1/2-ERK1/2 is essential for the induction of XRCC1 after exposure to radiation [12]. However, whether ERK1/2 and AKT signals involve in regulating XRCC1 expression upon etoposide treatment and its role in the etoposide-induced cytotoxicity in NSCL...

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Resveratrol chemosensitizes breast cancer cells to melphalan by cell cycle arrest

Cited by 70 publications

References 34 publications

Use of Grape Polyphenols Against Carcinogenesis: Putative Molecular Mechanisms of Action Using In Vitro and In Vivo Test Systems

Use of Grape Polyphenols Against Carcinogenesis: Putative Molecular Mechanisms of Action Using In Vitro and In Vivo Test Systems

The comparative study among different fractions of muscadine grape ‘Noble’ pomace extracts regarding anti-oxidative activities, cell cycle arrest and apoptosis in breast cancer

Resveratrol Enhances Etoposide‐Induced Cytotoxicity through Down‐Regulating ERK1/2 and AKT‐Mediated X‐ray Repair Cross‐Complement Group 1 (XRCC1) Protein Expression in Human Non‐Small‐Cell Lung Cancer Cells

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