Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer cell line

Osman, Amira; Bayoumi, Hadeel M.; Al-Harthi, Sameer E.; Damanhouri, Zoheir A.; Elshal, Mohamed F.

doi:10.1186/1475-2867-12-47

Cited by 71 publications

(64 citation statements)

References 24 publications

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“…Resveratrol was reported to enhance the cytotoxic effect of DOX on the growth of human breast cancer MCF-7 cells (Osman et al, 2012), however the mechanism was not fully understood. CBR1 was identified as a resveratrol-binding protein by affinity chromatography.…”

Section: The Inhibition Of Cbr1 By Polyphenolsmentioning

confidence: 99%

The modulation of carbonyl reductase 1 by polyphenols

Boušová

Skálová

Souček

et al. 2015

Drug Metabolism Reviews

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Carbonyl reductase 1 (CBR1), an enzyme belonging to the short-chain dehydrogenases/reductases family, has been detected in all human tissues. CBR1 catalyzes the reduction of many xenobiotics, including important drugs (e.g. anthracyclines, nabumetone, bupropion, dolasetron) and harmful carbonyls and quinones. Moreover, it participates in the metabolism of a number of endogenous compounds and it may play a role in certain pathologies. Plant polyphenols are not only present in many human food sources, but are also a component of many popular dietary supplements and herbal medicines. Many studies reviewed herein have demonstrated the potency of certain flavonoids, stilbenes and curcuminoids in the inhibition of the activity of CBR1. Interactions of these polyphenols with transcriptional factors, which regulate CBR1 expression, have also been reported in several studies. As CBR1 plays an important role in drug metabolism as well as in the protection of the organism against potentially harmful carbonyls, the modulation of its expression/activity may have significant pharmacological and/or toxicological consequences. Some polyphenols (e.g. luteolin, apigenin and curcumin) have been shown to be very potent CBR1 inhibitors. The inhibition of CBR1 seems useful regarding the increased efficacy of anthracycline therapy, but it may cause the worse detoxification of reactive carbonyls. Nevertheless, all known information about the interactions of polyphenols with CBR1 have only been based on the results of in vitro studies. With respect to the high importance of CBR1 and the frequent consumption of polyphenols, in vivo studies would be very helpful for the evaluation of risks/benefits of polyphenol interactions with CBR1.

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Section: The Inhibition Of Cbr1 By Polyphenolsmentioning

confidence: 99%

The modulation of carbonyl reductase 1 by polyphenols

Boušová

Skálová

Souček

et al. 2015

Drug Metabolism Reviews

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“…However, patients respond poorly to chemotherapy regimens combining folinic acid, 5-fluorouracil and either oxaliplatin (FOLFOX) or irinotecan mainly due to multidrug resistance, preventing the eradication of metastatic disease (5,6). Therefore, improvements in overcoming colorectal cancer chemoresistance are an urgent need and should be a focus of investigation.…”

Section: Introductionmentioning

confidence: 99%

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis

Herath

Devun

Lienafa

et al. 2016

Molecular Cancer Therapeutics

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Metastatic liver disease from colorectal cancer is a significant clinical problem. This is mainly attributed to nonresectable metastases that frequently display low sensitivities to available chemotherapies and develop drug resistance partly via hyperactivation of some DNA repair functions. Combined therapies have shown some disease control; however, there is still a need for more efficient chemotherapies to achieve eradication of colorectal cancer liver metastasis. We investigated the tolerance and efficacy of a novel class of DNA repair inhibitors, Dbait, in association with conventional chemotherapy. Dbait mimics double-strand breaks and activates damage signaling, consequently inhibiting single-and double-stranded DNA repair enzyme recruitment. In vitro, Dbait treatment increases sensitivity of HT29 and HCT116 colorectal cancer cell lines. In vivo, the pharmacokinetics, biodistribution and the efficacy of the cholesterol-conjugated clinical form of Dbait, DT01, were assessed. The chemosensitizing abilities of DT01 were evaluated in association with oxaliplatin and 5-fluorouracil in intrahepatic HT29 xenografted mice used as a model for colorectal cancer liver metastasis. The high uptake of DT01 indicates that the liver is a specific target. We demonstrate significant antitumor efficacy in a liver metastasis model with DT01 treatment in combination with oxaliplatin and 5-fluorouracil (mean: 501 vs. 872 mm 2 , P ¼ 0.02) compared to chemotherapy alone. The decrease in tumor volume is further associated with significant histologic changes in necrosis, proliferation, angiogenesis and apoptosis. Repeated cycles of DT01 do not increase chemotherapy toxicity. Combining DT01 with conventional chemotherapy may prove to be a safe and effective therapeutic strategy in the treatment of metastatic liver cancer. Mol Cancer Ther; 15(1); 15-22. Ó2015 AACR.

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“…Resveratrol exerts preventive effects against pathological processes such as inflammation (8), atherosclerosis (9), cardiovascular disease (10), type 2 diabetes (11), and tumorigenesis including breast cancer (12). Furthermore, resveratrol enhances the cytotoxic effect of the anticancer drug doxorubicin on the growth of breast cancer MCF-7 cells (13,14). However, its molecular mechanisms remain unclear.…”

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confidence: 99%

Resveratrol Reduces the Hypoxia-Induced Resistance to Doxorubicin in Breast Cancer Cells

Mitani

Ito

Harada

et al. 2014

J Nutr Sci Vitaminol

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Summary Resveratrol (3,4′,5-trihydroxy-trans-stilbene) is known to enhance the cytotoxicity of the anticancer drug doxorubicin. On the other hand, breast cancer MCF-7 cells acquire resistance to doxorubicin under hypoxic conditions. In this study, we investigated the effect of resveratrol on hypoxia-induced resistance to doxorubicin in MCF-7 cells. Resveratrol and its derivative 3,5-dihydroxy-4′-methoxy-trans-stilbene, but not 3,5-dimethoxy-4′-hydroxy-trans-stilbene, cancelled hypoxia-induced resistance to doxorubicin at a concentration of 10 mm. Carbonyl reductase 1 (CBR1) catalyzes the conversion of doxorubicin to its metabolite doxorubicinol, which is much less effective than doxorubicin. Hypoxia increased the expression of CBR1 at both mRNA and protein levels, and knockdown of CBR1 inhibited hypoxia-induced resistance to doxorubicin in MCF-7 cells. Knockdown of hypoxiainducible factor (HIF)-1a repressed the hypoxia-induced expression of CBR1. Resveratrol repressed the expression of HIF-1a protein, but not HIF-1a mRNA, and decreased hypoxiaactivated HIF-1 activity. Resveratrol repressed the hypoxia-induced expression of CBR1 at both mRNA and protein levels. Likewise, 3,5-dihydroxy-4′-methoxy-trans-stilbene decreased the hypoxia-induced expression of CBR1 protein, but not 3,5-dimethoxy-4′-hydroxy-transstilbene. Furthermore, resveratrol decreased the expression of HIF-1a protein even in the presence of the proteasome inhibitor MG132 in hypoxia. Theses results indicate that in MCF-7 cells, HIF-1a-increased CBR1 expression plays an important role in hypoxia-induced resistance to doxorubicin and that resveratrol and 3,5-dihydroxy-4′-methoxy-trans-stilbene decrease CBR1 expression by decreasing HIF-1a protein expression, perhaps through a proteasome-independent pathway, and consequently repress hypoxia-induced resistance to doxorubicin.

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Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer cell line

Cited by 71 publications

References 24 publications

The modulation of carbonyl reductase 1 by polyphenols

The modulation of carbonyl reductase 1 by polyphenols

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis

Resveratrol Reduces the Hypoxia-Induced Resistance to Doxorubicin in Breast Cancer Cells

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