Resveratrol improves the anticancer effects of doxorubicin in vitro and in vivo models: A mechanistic insight

Rai, Girish; Mishra, Sanjay; Suman, Shankar; Shukla, Yogeshwer

doi:10.1016/j.phymed.2015.12.020

Cited by 112 publications

(69 citation statements)

References 33 publications

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“…47 Furthermore, REV enhances the anticancer effects of doxorubicin in breast cancer cells. 48 In the present study, we showed that REV inhibits the Hippo/YAP signaling pathway, leading to the downregulation of YAP target gene expression and consequent attenuation of breast cancer cell invasion. We observed that REV reduces the LPA- and EGF-induced expression of AREG, CTGF and CYR61.…”

Section: Discussionmentioning

confidence: 50%

Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis

et al. 2017

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Hippo/YAP signaling is implicated in tumorigenesis and progression of various cancers. By inhibiting a plethora signaling cascades, resveratrol has strong anti-tumorigenic and anti-metastatic activity. In the present study, we demonstrate that resveratrol decreases the expression of YAP target genes. In addition, our data showed that resveratrol attenuates breast cancer cell invasion through the activation of Lats1 and consequent inactivation of YAP. Strikingly, we also demonstrate that resveratrol inactivates RhoA, leading to the activation of Lats1 and induction of YAP phosphorylation. Further, resveratrol in combination with other agents that inactivate RhoA or YAP showed more marked suppression of breast cancer cell invasion compared with single treatment. Collectively, these findings indicate the beneficial effects of resveratrol on breast cancer patients by suppressing the RhoA/Lats1/YAP signaling axis and subsequently inhibiting breast cancer cell invasion.

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Section: Discussionmentioning

confidence: 50%

Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis

et al. 2017

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“…The latter pro-survival role appears to be the effect of the constitutively-elevated autophagy rate of MDA-MB-231 cells [14]. In fact, various publications have demonstrated that inhibition of autophagy in this cell line leads to sensitization to the lethal effect of chemicals and apoptosis activation [14,26,27]. In this paper we have checked whether the drugs under study might modulate the autophagic rate by two different approaches, i.e., the flow cytometric evaluation of AVO accumulation in conjunction with the immunorevelation of the protein marker beclin-1 [28], which is a key component of autophagy machinery belonging to the signal-initiating class III phosphatidylinositol-3 kinase complex [29].…”

Section: Discussionmentioning

confidence: 99%

Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells

Librizzi

Spencer

Luparello

2016

IJMS

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We examined the effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) combined with the vascular endothelial growth factor receptor-1/2 inhibitor (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one on MDA-MB-231 breast cancer cells (triple-negative) in the form of both a cocktail of the separate compounds and a chemically synthesized hybrid (N-hydroxy-N'-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-5-yl]octanediamide). Comparative flow cytometric and Western blot analyses were performed on cocktail- and hybrid-treated cells to evaluate cell cycle distribution, autophagy/apoptosis modulation, and mitochondrial metabolic state in order to understand the cellular basis of the cytotoxic effect. Cell cycle analysis showed a perturbation of the rate of progression through the cycle, with aspects of redistribution of cells over different cycle phases for the two treatments. In addition, the results suggest that the two distinct classes of compounds under investigation could induce cell death by different preferential pathways, i.e., autophagy inhibition (the cocktail) or apoptosis promotion (the hybrid), thus confirming the enhanced potential of the hybrid approach vs. the combination approach in finely tuning the biological activities of target cells and also showing the hybrid compound as an additional promising drug-like molecule for the prevention or therapy of “aggressive” breast carcinoma.

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“…Doxorubicin (DOX) is a well-known, potent drug for the treatment of breast cancer patients [3], even though it displays adverse side-effects in terms of cardiotoxicity, hepatotoxicity nephrotoxicity, typhlitis, and other toxicities [4,5]. For advanced HCC treatment, doxorubicin (DOX), an anthracycline anticancer agent, has also been used frequently; however, it shows a maximum response rate of approximately 15–20% [6,7], which is not sufficient for HCC treatment.…”

Section: Introductionmentioning

confidence: 99%

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells

Saha

Yin

Kim

et al. 2017

IJMS

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Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer drug for various cancers, but the synergistic anti-cancer effect of VPA and doxorubicin (DOX) combination treatment and its potential underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC and identify a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.

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Resveratrol improves the anticancer effects of doxorubicin in vitro and in vivo models: A mechanistic insight

Cited by 112 publications

References 33 publications

Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis

Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis

Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells

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