Manuka honey synergistically enhances the chemopreventive effect of 5-fluorouracil on human colon cancer cells by inducing oxidative stress and apoptosis, altering metabolic phenotypes and suppressing metastasis ability

Afrin, Sadia; Giampieri, Francesca; Forbes‐Hernández, Tamara Y.; Gasparrini, Massimiliano; Amici, Adolfo; Cianciosi, Danila; Quiles, José L.; Battino, Maurizio

doi:10.1016/j.freeradbiomed.2018.07.014

Cited by 71 publications

(43 citation statements)

References 53 publications

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“…In spite of the extensive antitumor effect and the improved liver functions imposed by 5-FU, our results indicated that 5-FU group showed a marked elevation in hepatic content of MDA and a marked attenuation of hepatic GSH content when compared with normal control group. Such results were in consonance with results of earlier researches which indicated that 5-FU exerted some of its cytotoxic effects against tumor cells via production of ROS and induction of oxidative stress [40,41].…”

Section: Discussionsupporting

confidence: 91%

Hesperetin upregulates Fas/FasL expression and potentiates the antitumor effect of 5-fluorouracil in rat model of hepatocellular carcinoma

Aboismaiel

El-Mesery

El-Karef

et al. 2020

Egyptian Journal of Basic and Applied Sciences

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This study aimed to investigate the antitumor efficacy of hesperetin (HST) either alone or combined with 5-fluorouracil (5-FU) in thioacetamide (TAA)induced hepatocellular carcinoma (HCC) in rats. Moreover, possible HST molecular mechanism(s) of action were investigated. Sixty male Sprague-Dawley rats were randomized into six groups (n = 10/group); normal control (no treatment), HCC (TAA), HCC/carboxymethyl cellulose (CMC) (TAA+CMC), HST (TAA+HST in CMC), 5-FU (TAA+5-FU), HST/5-FU (TAA+HST+5-FU). Serum levels of liver enzymes (ALT and AST), bilirubin, albumin, total protein and alpha-Fetoprotein (AFP) along with hepatic contents of hepatic glutathione and mal0ndialdhyde were measured. Gene expression of Fas, FasL, caspase-8, caspase-3 and Bcl-2 were measured using real-time polymerase chain reaction. Histopathological examination was used to assess nodule size, fibrosis ratio and necroinflammatory score. HST showed improvements in hepatic functions, decreased levels of AFP and oxidative stress and restricted HCC progression. HST activated apoptosis through inducing Fas and FasL and inhibiting Bcl-2 gene expressions. Furthermore, HST/5-FU combination surpassed the results obtained from either HST or 5-FU groups. In conclusion, HST exerted its antitumor effect through induction of Fas/FasL apoptotic pathway and reduction of oxidative stress. HST and 5-FU combination provided prominent synergistic effects, thus it can be regarded as promising combination therapy for HCC.

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Section: Discussionsupporting

confidence: 91%

Hesperetin upregulates Fas/FasL expression and potentiates the antitumor effect of 5-fluorouracil in rat model of hepatocellular carcinoma

Aboismaiel

El-Mesery

El-Karef

et al. 2020

Egyptian Journal of Basic and Applied Sciences

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“…In conclusion, although honey has potential anti-PDAC benefits, its consumption should best be moderated. Nevertheless, for those patients with an irresistible ‘sweet tooth’, an occasional small spoonful of honey, especially Manuka honey, would be acceptable and may even potentiate the effectiveness of chemotherapy [ 175 , 176 ].…”

Section: Dietary Considerationsmentioning

confidence: 99%

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

Jentzsch

Davis

Djamgoz

2020

Cancers

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The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating ‘western’ clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main ‘hallmarks of cancer’. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chemotherapy with the two sub-groups of complementary agents alternately in weekly cycles. The review concludes that integrated management currently offers the best patient outcome. Opportunities to be investigated in the future include emerging modalities, precision medicine, the nerve input to tumors and, importantly, clinical trials.

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“…Bee products have been extensively evaluated for their effect on the proliferation of different cancer cells [7][8][9]. Furthermore, it has been demonstrated that propolis, a natural product produced by honeybee, has an interesting anticancer potential according to its chemical composition [10,11], which essentially depends on the geographical zone of collection [12].…”

Section: Introductionmentioning

confidence: 99%

Cuban Brown Propolis Interferes in the Crosstalk between Colorectal Cancer Cells and M2 Macrophages

et al. 2020

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Tumor-associated macrophages (TAMs), primarily the M2 phenotype, are involved in the progression and metastasis of colorectal cancer (CRC). Cuban brown propolis (Cp) and its main component Nemorosone (Nem) displays an antiproliferative effect on different cancer cells, including CRC cell lines. However, whether Cp and Nem could exploit its effect on CRC cells by targeting their relationship with TAMs remains to be elucidated. In this study, we differentiated the human monocytic THP-1 cells to M2 macrophages and confirmed this transition by immunofluorescence (IF) staining, qRT-PCR and zymography. An MTT assay was performed to determine the effect of Cp and Nem on the viability of CRC HT-29 cells co-cultured with M2 macrophages. Furthermore, the migration and invasion abilities of HT-29 cells were determined by Transwell assays and the expression levels of epithelial–mesenchymal transition (EMT) markers were analyzed by IF staining. We demonstrated that Cp and Nem reduced the viability of M2 macrophages and, accordingly, the activity of the MMP-9 metalloprotein. Moreover, we demonstrated that M2 macrophages produce soluble factors that positively regulate HT-29 cell growth, migration and invasion. These M2-mediated effects were counteracted by Cp and Nem treatments, which also played a role in regulating the expression of the EMT markers E-cadherin and vimentin. Taken together, our results indicate that Nem contained in Cp interferes in the crosstalk between CRC cells and TAMs, by targeting M2 macrophages.

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Manuka honey synergistically enhances the chemopreventive effect of 5-fluorouracil on human colon cancer cells by inducing oxidative stress and apoptosis, altering metabolic phenotypes and suppressing metastasis ability

Cited by 71 publications

References 53 publications

Hesperetin upregulates Fas/FasL expression and potentiates the antitumor effect of 5-fluorouracil in rat model of hepatocellular carcinoma

Hesperetin upregulates Fas/FasL expression and potentiates the antitumor effect of 5-fluorouracil in rat model of hepatocellular carcinoma

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

Cuban Brown Propolis Interferes in the Crosstalk between Colorectal Cancer Cells and M2 Macrophages

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