Antineoplastic activity of honey in an experimental bladder cancer implantation model: <i>In vivo</i> and <i> in vitro</i> studies

Sadek, Tarek; Miyanaga, Naoto; Onozawa, Mizuki; Hattori, Kazunori; Kawai, Koji; Shimazui, Toru; Akaza, Hideyuki

doi:10.1046/j.0919-8172.2003.00602.x

Cited by 156 publications

(119 citation statements)

References 9 publications

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“…Bladder cancer remains one of the main malignancies that affect the genitourinary tract 37, 38. The main clinical treatment is surgical resection assisted by chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer

Tao

Tang

et al. 2018

J Cellular Molecular Medi

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Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non‐muscle‐invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down‐regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p‐AMPK and p‐STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan‐Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in bladder cancer cells and tissues, and down‐regulation of PKM2 enhanced the sensitivity of THP in vitro. Activation of AMPK is essential for THP to exert anti‐bladder cancer activities. On the other hand, down‐regulating PKM2 activates AMPK and inhibits STAT3, correlated with THP sensitivity. Compared with THP alone (400 μmol L−1, 50 μL), the combination with metformin (60 mmol L−1, 50 μL) stopped growth of bladder cancer completely in vivo (combination group VS normal group P = .078). Down‐regulating the expression of PKM2 enhances the anticancer efficiency of THP. This study provides a new insight for improving the chemotherapeutic effect of THP.

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“…Bladder cancer remains one of the main malignancies that affect the genitourinary tract 37, 38. The main clinical treatment is surgical resection assisted by chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer

Tao

Tang

et al. 2018

J Cellular Molecular Medi

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“…The accumulation of cell population in G 0 /G 1 phase was also observed in other cancer cell lines after honey or chrysin treatments. Honeyinduced cell growth inhibition through accumulation of cell population in G 1 phase was also observed in T24 bladder cancer cell lines (32). Chrysin-induced G1 arrest in C6 glioma cells has been demonstrated to be caused by increased p21…”

Section: Discussionmentioning

confidence: 88%

Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression

Canini¹

2010

Int J Oncol

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Abstract. Honey has long been used in medicine for different purposes. Only recently, however, its antioxidant property and preventive effects against different diseases, such as cancer, have been highlighted. Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in acacia honey. It has previously been shown to be an anti-tumor agent. In this study, we investigated the antiproliferative role of honey or chrysin on human (A375) and murine (B16-F1) melanoma cell lines. The results of the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and the trypan blue exclusion test showed that both the tested compounds were able to induce an antiproliferative effect on melanoma cells in a dose-and time-dependent manner. Flow cytometry analysis indicated that cytotoxicity induced by honey or chrysin was mediated by G 0 /G 1 cell cycle arrest and induction of hyperploid progression. Our results suggest that the anti-proliferative effects of honey are due mainly to the presence of chrysin. Chrysin may therefore be considered a potential candidate for both cancer prevention and treatment. Further investigation is needed to validate the contribution of chrysin in tumor therapy in vivo.

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“…High phenolic and hydroxylmethylfurfural (HMF) contents of honey resulted in the growth inhibitory effects of cancer cells [30], and flavonoids have been reported to induce cell death of various cancer cell lines [31]. It has previously been reported that a Japanese pure unfractionated honey significantly reduced the proliferation of the human bladder cancer cells, T24 [32]. It has been reported that other type honey shows no significant cytotoxic effect on normal human cell lines [33].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore we hypothesize that acacia honey mediated inhibitory effects of cell growth of PC-3 cells might be due to perturbation in the cell cycle, which may possibly lead to programmed cell death. The antiproliferative effect of honey on human (A375) and murine (B16-F1) melanoma cell lines was found to be mediated by G0/G1 cell cycle arrest and induction of hyperploid progression [22,14].…”

Section: Discussionmentioning

confidence: 99%

“…It is a promising antitumor agent with pronounced anti-metastatic and anti-angiogenic effects [10], antibacterial, anti-inflammatory, immune-stimulant, antiulcer and wound/burn healing effects [11]. Various signaling pathways, including stimulation of tumor necrosis factor-alpha (TNF α) release, inhibition of cell proliferation, induction of apoptosis and cell cycle arrest, as well as inhibition of lipoprotein oxidation, mediate the beneficial effects exerted by honey and its major components such as chrysin and other flavonoids [12][13][14][15][16]. However, chronic consumption of honey that was mixed with rat pellets has been shown to have a positive impact on the architecture and integrity of hepatocytes in vivo [17].…”

Section: Introductionmentioning

confidence: 99%

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Acacia Honey Modulates Cell Cycle Progression, Pro-inflammatory Cytokines and Calcium Ions Secretion in PC-3 Cell Lines

et al. 2012

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Background: Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related deaths. Honey has been proven to have a potentiality of being among the functional foods by both in vivo and in vitro studies. Aim:This study was primarily designed to provide evidence on the apoptotic role of acacia honey on PC-3 cell line. Methods:MTT and mitotic index assay were used to determine the anti-proliferative effects. Cell cycle analysis was conducted on flow cytometer using propidium iodide. Expression of pro-inflammatory cytokines [TNF α and IL 1β] and prostate specific antigen were determined by ELISA kits. Calcium ion level was analyzed by colorimetric method. Results:Our results show the anti-proliferative effects of acacia honey on NIH/3T3 and PC-3 cell lines with the IC 50 of 3.7 and 1.9% [v/v] respectively with simultaneous increase in the secretion of calcium ion and down regulation of prostate specific antigen. Significant [p < 0.05] dose-dependent modulation of G0/G1 phase was observed as compared with the control. However, there was an inverse relationship between TNF-α and IL-1β with latter being up regulated. Mitotic index of PC-3 cells decreased as the concentration of honey increases. Conclusion:Apoptotic role of acacia honey on PC-3 cell line may be due to modulation of G0/G1 phase, proinflammatory cytokines, calcium ions secretion and down regulation of prostate specific antigen in vitro.

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Antineoplastic activity of honey in an experimental bladder cancer implantation model: In vivo and in vitro studies

Cited by 156 publications

References 9 publications

Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer

Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer

Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression

Acacia Honey Modulates Cell Cycle Progression, Pro-inflammatory Cytokines and Calcium Ions Secretion in PC-3 Cell Lines

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