Chemomodulation of the antioxidative enzymes and peroxidative damage in the colon of 1,2‐dimethyl hydrazine‐induced rats by ellagicacid

Umesalma, Syed; Sudhandiran, Ganapasam

doi:10.1002/ptr.2962

Cited by 21 publications

(15 citation statements)

References 49 publications

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“…Cyclin D1 has been implicated in controlling the G1/S cell cycle transition and perhaps the most important checkpoint in the mammalian cell cycle, which is frequently overexpressed in human colon adenocarcinomas [38,39]. In our work, EA significantly decreased the levels of cyclin D1, might be attributed to its antioxidant property [40]. Thus, it can be concluded that EA attenuates proliferation of colon carcinoma HCT-15 cells by inhibiting PCNA and cyclin D1 as revealed by immunoblot, thereby showing its antiproliferative effect [16].…”

Section: Discussionmentioning

confidence: 52%

Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells

2014

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Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of human cancer. Ellagic acid (EA) has been known for its chemopreventive activity against various cancers and numerous investigations have shown its apoptotic activity both in vivo and in vitro. The present study was focused to elucidate the anticancerous effect and the mode of action of EA against HCT-15 colon adenocarcinoma cells. Cell viability was assessed using trypan blue assay at different concentrations. EA also promoted cell cycle arrest substantially at G2/M phase in HCT-15 cells. The activities of alkaline phosphatase and lactate dehydrogenase were decreased upon EA treatment, which shows the antiproliferative and the cytotoxic effects, respectively. The production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with EA. In further studies, EA inhibited proliferation-associated markers proliferating cell nuclear antigen and cyclin D1. The induction of apoptosis was accompanied by a strong inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway by EA. The expression of PI3K and pAkt was down-regulated in EA-treated cells, compared to normal cells. Further, EA promoted the expression of Bax, caspase-3, and cytochrome c, and suppression of Bcl-2 activity in HCT-15 cells that was determined by western blot analysis. Increased annexin V apoptotic cells and DNA fragmentation also accompanied EA-induced apoptosis. In conclusion, EA increased the production of ROS, decreased cell proliferation, and induced apoptosis in HCT-15 cells, and thus can be used as an agent against colon cancer.

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Section: Discussionmentioning

confidence: 52%

Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells

2014

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“…Group 3 rats received s.c. injection of 1,2-dimethylhydrazine (20 mg ⁄ kg body weight) once a week for 15 weeks and Group 4 rats were administered 1,2-dimethylhydrazine for the first 15 weeks followed by treatment with ellagic acid 60 mg ⁄ kg body weight, p.o. every day as reported earlier [16] for the remaining 15 weeks. After 30 weeks of experimental period, the rats were anaesthetized by diethyl ether and killed by cervical decapitation after an overnight fast.…”

Section: Methodsmentioning

confidence: 67%

“…We have reported that ellagic acid suppresses colon cancer in rats [16]; however, the precise mechanism by which ellagic acid mediates its action against colorectal cancer is not completely elucidated. Recent studies addressed its anti-inflammatory effect [25].…”

Section: Discussionmentioning

confidence: 99%

Differential Inhibitory Effects of the Polyphenol Ellagic Acid on Inflammatory Mediators NF‐κB, iNOS, COX‐2, TNF‐α, and IL‐6 in 1,2‐Dimethylhydrazine‐Induced Rat Colon Carcinogenesis

Umesalma

Sudhandiran

2010

Basic Clin Pharma Tox

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Dietary polyphenols have been found to possess preventive and therapeutic potential against several types of cancers. We investigated the effect of ellagic acid on colon cancer induced by 1,2-dimethylhydrazine in rats. Male Wistar albino rats were divided into four groups. Group 1 served as control, group 2 rats received ellagic acid 60 mg ⁄ kg bodyweight ⁄ every day p.o. throughout the experiment. Rats from groups 3 and 4 were given subcutaneous (s.c.) injections of 1,2-dimethylhydrazine (20 mg ⁄ kg body weight) once a week for the first 15 weeks; rats in group 4 received ellagic acid as in group 2 after the last injection of 1,2-dimethylhydrazine and continued till the end of the experimental period of 30 weeks. 1,2-dimethylhydrazine-induced rats exhibited alterations in cancer tumour markers [5¢-nucleotidase (5¢-ND), gamma glutamyl transpeptidase (c-GT), carcinoembryonic antigen (CEA), alphafetoprotein (AFP) and cathepsin-D (CD)]; pathophysiological markers [alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and oral administration of ellagic acid restored the levels of these marker enzymes. Nuclear factor-kappa B (NF-jB) actively involved in the regulation of both pro-inflammatory proteins [inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)] and pro-inflammatory cytokines [tumour necrosis factor (TNF)-a and interleukin (IL)-6] and in our study 1,2-dimethylhydrazine-induced group exhibited elevated expressions of all these inflammatory proteins. Ellagic acid administration reduced the expressions of NF-jB, COX-2, iNOS, TNF-a and IL-6 as confirmed by immunohistochemical, immunoblot and immunofluorescence analysis during 1,2-dimethylhydrazineinduced colon carcinogenesis. In conclusion, ellagic acid demonstrates anti-inflammatory property by iNOS, COX-2, TNF-a and IL-6 down-regulation due to inhibition of NF-jB and exerts its chemopreventive effect on colon carcinogenesis.Colorectal cancer is one of the leading causes of tumourrelated deaths and despite its high prevalence, the underlying pathological mechanisms remain elusive [1]. The incidence in Asia was estimated to rank 3rd in both genders for all malignant diseases in 2008 [2]. Colorectal cancer is a multistep process affected by environmental and genetic factors, which leads to normal colonic epithelium to dysplasia followed by a benign precursor stage, the pre-malignant polyp and can progress to invasive disease. Besides a genetic pre-disposition, diet also determines the risk for colon cancer and predominantly diets rich in fruits and vegetables diminish the risk of the disease [3]. 1,2-Dimethylhydrazine-induced model is utilized frequently, as it is similar to histopathological and molecular characteristics of human colon cancer model [4]. 1,2-Dimethylhydrazine is metabolized in liver to form azoxymethane and methylazoxymethanol later on transported to colon via bile or blood to generate its ultimate carcinogenic metabolite, diazonium ion which elicits an oxidative stress by methylating biomolecules of colonic epithe...

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“…We observed the initial lesions of ACF and development of small adenoma in DMH control group, whereas only ACFs and polyps, but not adenomas, were noted in the rest of the groups. Also some studies showed that DMH administration had increased levels of TNF- α and IL-6 and decreased endogenous antioxidant enzyme levels [27]. …”

Section: Discussionmentioning

confidence: 99%

Iminoflavones Combat 1,2-Dimethyl Hydrazine-Induced Aberrant Crypt Foci Development in Colon Cancer

Prasad

Kawade

Jayashree

et al. 2014

BioMed Research International

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The aim of the present study was to evaluate the antitumor potential of iminoflavones in in vitro and in vivo anticancer models. Preliminary screening in various cancer cell lines revealed four potential iminoflavones out of which IMF-8 was taken based on its activity against colon cancer cells. This was further confirmed by observing the nuclear changes in the cells by AO/EB and Hoechst 33342 staining studies. In vivo activity was assessed by dimethyl hydrazine-(DMH-) induced colon cancer model in rats. Animals were administered DMH (20 mg/kg, b.w. for 10 weeks and 30 mg/kg b.w., i.p. for 10 weeks) and were supplemented with (IMF-8) iminoflavone-8 (200 mg/kg, p.o. for 14 days). Results showed that DMH induced 100% aberrant crypt foci (ACF) and polyps which were significantly reduced in the IMF-8 treated group. IMF-8 significantly increased the catalase and GSH levels whereas it reduced the TNF-α and IL-6 levels markedly which suggests the antioxidative and anti-inflammatory actions of flavonoids present in IMF-8. The histopathological images of the IMF-8 treated colon showed no signs of mucosal crypt abscess. These findings suggest that the semi-synthetic iminoflavones, IMF-8, effectively inhibit DMH-induced ACFs and colonic crypts by alleviating the oxidative stress and suppressing the inflammation.

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Chemomodulation of the antioxidative enzymes and peroxidative damage in the colon of 1,2‐dimethyl hydrazine‐induced rats by ellagicacid

Cited by 21 publications

References 49 publications

Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells

Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells

Differential Inhibitory Effects of the Polyphenol Ellagic Acid on Inflammatory Mediators NF‐κB, iNOS, COX‐2, TNF‐α, and IL‐6 in 1,2‐Dimethylhydrazine‐Induced Rat Colon Carcinogenesis

Iminoflavones Combat 1,2-Dimethyl Hydrazine-Induced Aberrant Crypt Foci Development in Colon Cancer

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