Carcinogenesis is the uncontrolled cellular growth acquiring the ability to invade and disrupt the normal functioning of the cells. Chemotherapy utilising the low molecular weight drugs remains an essential treatment in eradicating and inhibiting the malignant tumours. In the present study, an attempt was made to investigate the cytotoxic and genotoxic potential of Doxorubicin against MDA-MB 453 human mammary carcinoma cell lines grown in vitro. This study also aimed to elucidate the mechanisms underlying doxorubicin toxicity in MDA-MB 453 cells.
The cytotoxic potential of doxorubicin against these cells was measured by MTT and Trypan blue exclusion assays, while genotoxic effect by micronucleus assay. The apoptotic assay performed in this present study is the fluorescence microscopic analysis to determine the type of cell death undertaken by these cancer cells. From the MTT and Trypan blue assay, it was found that, DOX was found to be most effective against MDA-MB 453 cells and showed a dose dependent decline in cell with an IC50 value of about 10.1 and 2.5 µM after 3 and 24 hours respectively. Further, doxorubicin treatment caused a significant increase in the genotoxicity as evidenced by the concentration-dependent elevation in the micronucleated binucleate cells (MNBNC). Moreover, results of the micronuclei study indicated division delay in the proliferating cell population of DOX treated group by showing decrease in the cytokinesis blocked proliferation index. Results obtained from the fluorescence microscopic analysis has demonstrated the percentage increase in both the necrotic and apoptotic cells. To conclude, toxic effect of DOX in MDA-MB 453 cells may be attributed to multiple mechanisms such as induction of oxidative stress and genotoxic effect, ultimately leading to cell death by both apoptosis and necrosis.