Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats

Khan, Mahaboob S.; Devaraj, Halagowder; Devaraj, Niranjali

doi:10.1016/j.taap.2010.12.004

Cited by 81 publications

(51 citation statements)

References 35 publications

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“…GST-pi is clearly known to be a strong marker enzyme for rat preneoplastic lesions. 33,[35][36][37] In our study, protein and mRNA expressions of hepatic GST-pi were observed to increase in DEN-treated rats. Accordingly, our findings indicate that DEN treatment resulted in precancerous liver cirrhosis in rats.…”

Section: Discussionsupporting

confidence: 58%

“…2,7,34 In the current study, rats were injected with DEN (200 mg/kg; i.p.) three times with an interval of 15 days at 4, 6, and 8 weeks, as previously reported, 33,35 and sacrificed 8 weeks after the last Figure 3. The effects of blueberry (BB) supplementation on hepatic hepatic hydroxyproline (HYP) and malondialdehyde (MDA), diene conjugate, and protein carbonyl (PC) levels in diethylnitrosamine (DEN)-treated rats.…”

Section: Discussionmentioning

confidence: 63%

“…7,8,31,32 Repeated injections of DEN were found to cause significant fibrosis in 8-10 weeks and the existence of both cirrhosis and preneoplastic lesions in 12-16 weeks and HCC in 20 weeks. 2,8,9,32,33 Compared to the other models, reproduction of cirrhosis and HCC sequentially as similar to human liver disease becomes possible with this protocol and this may enable the usage of some agents to prevent the progression of cirrhosis to advanced stages. 2,7,34 In the current study, rats were injected with DEN (200 mg/kg; i.p.)…”

Section: Discussionmentioning

confidence: 99%

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Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats

Bingül

Başaran-Küçükgergin

Aydın

et al. 2016

Int J Immunopathol Pharmacol

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Diethylnitrosamine (DEN)-induced liver cancer normally develops in stages that progress from cirrhosis and carcinoma. Increased oxidative stress is suggested to play a role in DEN-induced carcinogenicity. Blueberries (BB) contain high antioxidant capacity. We investigated the effect of BB supplementation on development of DEN-induced cirrhosis and neoplastic lesions in the liver. Rats were injected with DEN (200 mg/kg; i.p.) three times with an interval of 15 days at 4, 6, and 8 weeks and sacrificed 8 weeks after the last DEN injection. They were also fed on 8% BB (w/w) containing chow for 16 weeks. Hepatic damage markers in serum were determined together with hepatic histopathological examinations. Hydroxyproline (HYP), malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and their mRNA expressions were measured. Protein and mRNA expressions of glutathione transferase-pi (GST-pi) were evaluated as a marker of preneoplastic lesions. BB supplementation decreased hepatic damage markers in serum and hepatic MDA, DC, and PC levels, but SOD, CAT, and GSH-Px activities and their mRNA expressions remained unchanged in DEN-treated rats. BB attenuated cirrhotic changes and decreased hepatic HYP levels and GST-pi expressions. Our results indicate that BB is effective in decreasing development of DEN-induced hepatic cirrhosis and preneoplastic lesions by acting as an antioxidant (radical scavenger) itself without affecting activities and mRNA expressions of antioxidant enzymes.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats

Bingül

Başaran-Küçükgergin

Aydın

et al. 2016

Int J Immunopathol Pharmacol

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“…[75] Chrysin administration significantly reduced the number and size of preneoplasic nodules and the expression of COX-2 and nuclear factor-kB and p65 in rats, whereas increased p53, Bax and caspase3 mRNA and protein levels were seen. Likewise, a decrease in levels of b-arrestin and the anti-apoptotic marker Bcl-xL was also noticed.…”

Section: Propolis and Experimental Carcinogenesismentioning

confidence: 89%

Cytotoxic constituents of propolis inducing anticancer effects: a review

Watanabe

Amarante

Conti

et al. 2011

Journal of Pharmacy and Pharmacology

185

133

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Objectives Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e.g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed. Key findings The effect of propolis on experimental carcinogenesis is discussed, as well as its possible mechanisms of action against tumours, involving apoptosis, cell cycle arrest and interference on metabolic pathways. Propolis seems to be efficient against different tumour cells both in vitro and in vivo, which suggests its potential in the development of new anticancer drugs. Summary Propolis extracts may be important economically and would allow a relatively inexpensive cancer treatment. Preclinical investigations are needed to further elucidate the benefits of propolis and its antitumour properties.

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“…Their role has been already proved in the development of malignancy. 11 One of the various cellular processes that regulate the induction and execution of the chemicalinduced carcinogenesis is the activation of protein kinases, including protein kinase C, which is capable of the stimulation of several cell cycle progression molecules, such as p38 MAPK.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Augmented Immune Surveillance and Tumor Cell Death by Cytoplasmic Stabilization of p53 as a Chemopreventive Strategy of 3 Promising Medicinal Herbs in Murine 2-Stage Skin Carcinogenesis

Ali

Khan

et al. 2013

Integr Cancer Ther

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Cancer is the final outcome of a plethora of events. Targeting the proliferation or inducing programmed cell death in a proliferating population is a major standpoint in the cancer therapy. However, proliferation is regulated by several cellular and immunologic processes. This study reports the inhibition of proliferation by augmenting immune surveillance, silencing acute inflammation, and inducing p53-mediated apoptosis of skin cancer by 3 promising medicinal extracts. We used the well-characterized model for experimental skin carcinogenesis in mice for 32 weeks to study the chemopreventive effect of the methanolic extracts of Trigonella foenumgraecum, Eclipta alba, and Calendula officinalis. All 3 extracts reduced the number, incidence, and multiplicity of tumors, which was confirmed by the pathologic studies that showed regressed tumors. There was a significant reduction in the PCNA+ nuclei in all treatment groups 32 weeks after the initiation. Mechanistic studies revealed that proliferative population in tumors is diminished by the restoration of the endogenous antioxidant defense, inhibition of the stress-related signal-transducing element NFκB, reduction of inflammation, enhancement of immunosurveillance of the genetically mutated cells, along with silencing of the cell cycle progression signals. Finally, all 3 medicinal extracts induced stable expression of p53 within the tumors, confirmed by the CFDA-Cy3 apoptosis assay. Results of our study confirm that these extracts not only limit the rate of proliferation by inhibition of the processes integral to cancer development but also induce stable cytoplasmic expression of p53-mediated apoptosis, leading to fewer and regressed tumors in mice.

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Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats

Cited by 81 publications

References 35 publications

Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats

Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats

Cytotoxic constituents of propolis inducing anticancer effects: a review

Assessment of Augmented Immune Surveillance and Tumor Cell Death by Cytoplasmic Stabilization of p53 as a Chemopreventive Strategy of 3 Promising Medicinal Herbs in Murine 2-Stage Skin Carcinogenesis

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