Elsevier

Toxicology in Vitro

Volume 22, Issue 3, April 2008, Pages 625-631
Toxicology in Vitro

Antigenotoxic effect of apigenin against anti-cancerous drugs

https://doi.org/10.1016/j.tiv.2007.12.002Get rights and content

Abstract

Mitomycin C and cyclophosphamide are well known anti-tumor drugs. Their genotoxic effects are well established in various test systems. The genotoxic effects in non-tumor cell are of special significance due to the possibility that they may induce secondary tumors in cancer patients. Apigenin is a well known anti-oxidant and possess number of properties that are beneficial in someway to humans. With this view, the present study deals with the effect of apigenin against the genotoxic doses of mitomycin C and cyclophosphamide using chromosomal aberrations, sister chromatid exchanges and cell cycle kinetics as a parameters. The treatment of apigenin results in a significant, dose dependent decrease in the genotoxic damage, induced by mitomycin C and cyclophosphamide. It is concluded that the apigenin is potent in reducing the genotoxic damage, induced by anti-cancerous drugs, thereby reducing the chances of developing secondary tumors during the therapy.

Introduction

Apigenin is one of the several active ingredients found naturally in many fruits and vegetables, including apples and cerlery. It is found in several popular spices, including basil, oregano, tarragon, cilantro and parsley. A high amount of apigenin is found in parsley, peppermint, lemon, berries and fruits (Peterson and Dwyer, 1998). It is a member of flavone family of the flavonoid. Apigenin is recognized in traditional or alternative medicine for its pharmacological activity (Hoftman, 2000). In the reverse mutation assay, apigenin was negative in Salmonella typhimurium strains TA97, TA98, TA100, TA102, TA1535 and TA1538 with and without metabolic activation by liver S9 microsomal fraction (NLM, 2000). The mutagenic activity of apigenin in Escherichia coli was examined and it weakly induced SOS repair system in E. coli K-12 strain PQ37 with and without metabolic activation (Czeczot and Bilbin, 1991). Apigenin possess anti-inflammatory effects, free radical scavenging and anti-carcinogenic effects (Kim et al., 1998, PHS-149, 1972). It has been shown to possess growth inhibitory properties in several cancer lines including breast, colon, skin, thyroid leukemia cells and pancreatic (Yin et al., 2001, Yin et al., 1999, Wang et al., 2000, Caltagirone et al., 2000, Taka-hashi et al., 1998, Ujiki et al., 2006), tumor inhibition (Wei et al., 1990, Li et al., 1996) and enzyme inhibitory properties (Wei et al., 1990, Jeong et al., 1992).

There is much evidence for anti-carcinogenic activity of apigenin but less is known about its antigenotoxicity which is limited to mice (Khan et al., 2006). The present study was aimed to study the antigenotoxic effects of apigenin in both absence as well as presence of metabolic activation (S9 mix) system. Mitomycin C was used as positive control for the absence of metabolic activation experiments and cyclophosphamide act as a positive control for the metabolic activation experiments. The treatments with apigenin results in a significant, dose dependent decrease in the genotoxic damage, induced by mitomycin C and cyclophosphamide thereby, reducing the chances of developing secondary tumors during the chemotherapy.

Section snippets

Chemical

Apigenin (CAS: 520-36-5; Sigma); RPMI 1640, fetal calf serum, phytohaemagglutinin-M, antibiotic–antimycotic mixture (Gibco); dimethylsulphoxide, 5-bromo-2-deoxyuridine, colchicine (SRL, India), Giemsa stain (Merck). Mitomycin C (CAS No: 50-07-7) cyclophosphamide (CAS No: 6055-19-2).

Human lymphocyte culture

Duplicate peripheral blood cultures of two female donors were treated according to Carballo et al. (1993). Briefly, heparinized blood sample (0.5 ml), was obtained from a healthy female donor and was placed in a

Results

In chromosomal aberration analysis, treatment with mitomycin C alone resulted in a significant increase of chromosomal aberrations. A significant decrease in number of abnormal cells were observed when 6 μM of mitomycin C was used separately with different dosages of apigenin, i.e., 1, 5, 10 and 20 μM (Table 1). Similar results were obtained for the cyclophosphamide (CP) treatment, with the different dosages of apigenin (Table 2). In sister chromatid exchange analysis, a significant increase in

Discussion

Our study clearly demonstrates the antigenotoxic potential of apigenin both in the absence as well as presence of metabolic activation (S9 mix) systems. The selected doses of apigenin were not genotoxic, however at 93 μM, an increase in micronucleus frequency was reported in human lymphocytes in vitro (Rithidech et al., 2005). A study conducted by Snyder and Gillies (2002) also showed clastogenic activity of apigenin at 100 μM in Chinese hamster V79 cells, and proposed that clastogenic activity

Acknowledgements

Thanks are due to the CSIR, New Delhi for the fellowship No. 9/112(355)/2003-EMR to the author (Y.H.S.) and to the Chairman, Department of Zoology, A.M.U., Aligarh for the laboratory facilities.

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