Antiproliferative and apoptotic-inducing potential of ellagic acid against 1,2-dimethyl hydrazine-induced colon tumorigenesis in Wistar rats

Abstract

Colon cancer remains one of the major worldwide causes of cancer-related morbidity and mortality in Western countries and is increasingly common in Asia. Ellagic acid (EA), a major component of polyphenol possesses attractive remedial features. The aim of this study is to divulge the potential effect of EA during 1,2-dimethyl hydrazine (DMH)-induced colon cancer in male Wistar albino rats. The rats were segregated into four groups: group I, control rats; group II, rats received EA (60 mg/kg b.wt./day, orally); rats in group III, induced with DMH (20 mg/kg b.wt.) subcutaneously for 15 weeks; DMH-induced group IV rats were initiated with EA treatment. Colon of the rats treated with DMH exhibited higher glycoconjugates and proliferation index such as elevated expressions of argyrophilic nucleolar organizing regions (AgNORs), proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteins (MMP-2 and -9), and mast cells. DMH induction also increased phase I-metabolizing enzymes with simultaneous decrease in the phase II detoxifying enzymes. In contrast, dietary administration of EA significantly (p < 0.05) down regulated the proliferation index and restored back the levels of biotransformation enzymes. The carcinogenic insult also altered the expression of pro-apoptotic protein p53, whereas dietary EA administration significantly (p < 0.01) up regulates p53 expression to further induce apoptotic pathway. Ultrastructural changes in colon were also in accord with the above aberrations. Overall findings suggested that the suppression of colon cancer by EA in vivo involves inhibition of cell proliferation, activation of apoptosis, and efficient detoxification.

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

“…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].…”

“…The present study was focused to address the cytotoxic effects of EA on HCT-15 cells. We demonstrated that EA promoted p53 gene expression [16] and inhibited cyclin D1 gene expression, and therefore may lead to G2/M phase arrest in the cell cycle. EA has been demonstrated to exhibit antineoplastic activity, through induction of apoptosis [14,16] and cell cycle arrest.…”

“…We demonstrated that EA promoted p53 gene expression [16] and inhibited cyclin D1 gene expression, and therefore may lead to G2/M phase arrest in the cell cycle. EA has been demonstrated to exhibit antineoplastic activity, through induction of apoptosis [14,16] and cell cycle arrest. Many studies have reported that cyclin D1 and cyclin-E are involved in the cell cycle from G1 into S-phase, and our results showed that EA inhibited Cyclin D2, which may be the mechanism resulting in G2/M arrest in the cell cycle of HCT-15 cells.…”

“…EA-induced apoptosis in many human cancer cell lines such as bladder T24, breast MCF-7, prostate DU 145, and leukemia MOLT-4 cells [11][12][13]. Furthermore, EA is reported to induce apoptosis in vivo [14] and exert anti-inflammatory [15], and antiproliferative properties [16]. Despite these pharmacological benefits and activities of EA in vitro, the molecular effects by EA provokes apoptosis in human colon adenocarcinoma HCT-15 cells are still not investigated.…”

Rosuvastatin and ellagic acid protect against isoproterenol-induced myocardial infarction in hyperlipidemic rats

“…In such report, ellagic acid was administered in smaller doses (7.5 & 15 mg/kg/day) for a shorter period (10 days), which could account for the disagreement with our study. In addition, the Bax discrepancy could be explained based on the reported apoptosis-inducing activity of ellagic acid on cancer (Han et al, 2006;Umesalma et al, 2014).…”