Abstract

Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to ~5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy.

Highlights

  • Occurring compounds are considered as the most interesting agents to test for cancer prevention and therapy, due to their anticipated multimodal actions and limited toxicity

  • Cytotoxic effect of quercetin and ellagic acid was examined in three leukemic cell lines (CEM, K562 and Nalm6), two breast cancer cell lines (T47D and Ehrlich Ascites Carcinoma (EAC)) and two normal cell lines (293T and MEF1)

  • Cells were treated with increasing concentration of quercetin and ellagic acid (10, 50, 100 and 250 μM for 48 h) and cytotoxic effect was assessed by either MTT or trypan blue, and in some cases both

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Summary

Introduction

Occurring compounds are considered as the most interesting agents to test for cancer prevention and therapy, due to their anticipated multimodal actions and limited toxicity. Among various naturally occurring compounds, polyphenols are known to be present in various edible fruits including grapes, berries, walnut, pomegranate, apples, etc. The ability of quercetin to induce cell cycle arrest warrants additional investigation as conflicting findings have been reported. Ellagic acid is one of the phenolic compounds abundantly present in fruits and nuts and is reported to inhibit cell mobility and cell invasion Quercetin has been used in combination with many naturally occurring compounds like resveratrol1, 2-methoxyestradiol[17], luteolin derivatives[18], ellagic acid[2], as well as synthetic drugs used in chemotherapy e.g., doxorubicin[19], cisplatin[20] etc. Combination therapy with quercetin resulted in the synergistic effects as well[1,17,21]

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