Alteration in the Doxorubicin-Induced DNA Damage in Cultured V79 Cells by Aegle marmelos (L.) Correa (Bael): A Comet Assay Study

Ganesh Chandra Jagetia

doi:10.4172/2376-0281.1000190

Abstract

The clinical applicability of wide spectrum chemotherapeutic drug, doxorubicin is limited due to induction of severe cardiomyopathy resulting from DNA damage. The present study was aimed to evaluate the protective effect of bael (Aegle marmelos) extract (AME) on the doxorubicin-induced molecular DNA damage in V79 cells. V79 (Chinese hamster lung fibroblasts) cells were treated with 0 or 25 μg/ml AME before exposure to 0, 1, 2.5, 5, 10, 25 or 50 μg/ml doxorubicin DOX. The DNA damage was studied at different post-doxorubicin treatment times using single cell gel electrophoresis. Doxorubicin caused a maximum DNA damage at 1 h post-DOX treatment indicated by a highest Olive Tail Movement (OTM) and tail DNA, whereas treatment of V79 cells with 25 μg/ml AME enhanced DNA repair at all assessment times with a maximum repair up to 6 h which did not alter thereafter. In another experiment DOX caused a concentration dependent increase in the DNA damage and treatment of V79 cells with 25 μg/ml AME significantly inhibited DOX-induced DNA damage at all post-DOX treatment times. The rate of DNA repair was higher in AME pre-treated cells than DOX-treatment alone. Assessment of cell survival showed a concentration dependent decline in the clonogenicity after DOX-treatment, whereas AME pre-treatment arrested the DOX-induced reduction in the cell survival. The DNA damage and clonogenicity of cells showed a close but inverse relationship, i.e., with increasing DNA damage there was a corresponding reduction in the cell survival. This relationship between cell survival and DNA damage was linear quadratic. Our study demonstrates that AME pretreatment reduced the DOX-induced DNA damage and hastened the DNA repair in V79 cells, thus demonstrating the chemoprotective potential of AME.

Highlights

Doxorubicin, an antibiotic having a wide spectrum of anti-neoplastic activity was isolated from the cultures of mutant fungus, Streptomyces peucetius caesius [1]
The results of clonogenic survival are expressed as surviving fraction in Figure 2, whereas DNA damage are expressed in Tables 1 and 2 and Figures 3 and 4
Treatment of V79 cells with 25 μg/ml AME before exposure to different concentrations of Doxorubicin hydrochloride (DOX) resulted in an elevation in the cell survival when compared with the DOX treatment alone (Figure 2)

Summary

Introduction

Doxorubicin (adriamycin), an antibiotic having a wide spectrum of anti-neoplastic activity was isolated from the cultures of mutant fungus, Streptomyces peucetius caesius [1]. It has been found to be active against several solid neoplasms [2], Hodgkin's disease, leukemias, lymphomas [3] and rat tumors [4]. Despite the fact that doxorubicin is active against several tumors it causes severe cardiomyopathy limiting its clinical use [5]. In an attempt to control neoplastic disorders and distant metastases the chemotherapeutic agents are administered systemically, which adversely affects the DNA of other normal cells leading to genotoxicity and subsequently producing second malignancies [16,17]. Since doxorubicin is a wide spectrum chemotherapeutic drug, reduction in its toxicity will be beneficial in the better management of neoplasia and benefit the patients receiving doxorubicin therapy

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Results

Discussion

Conclusion