Gene expression and histopathology alterations during rat mammary carcinogenesis induced by 7,12- dimethylbenz[a]anthracene and the protective role of Neem (Azadirachta indica) leaf extract

Abstract

Abstract: The present study was investigated to evaluate the protective role of ethanolic neem leaf extract (ENLE) against 7,12-dimethylbenz[a]anthracene (DMBA)-induced expression alterations of the Bcl-2, CK8, CK19, p53, p21, p27 and PCNA genes and histopathological lesions in the mammary tissues of female rats. Eighty Swiss albino female rats were divided into eight groups. Group 1 supplemented with corn oil as control. Group 2 females received DMBA. Groups 3, 4 and 5 females received 100, 200 and 400 mg/kg of ENLE alternate to the DMBA application from the beginning of the experimental period, respectively. Groups 6, 7, and 8 females treated similar to groups 3, 4 and 5 plus DMBA. All the animals were sacrificed after an experimental period of 12 weeks. The expression of Bcl-2, CK8, CK19, p53, p21, p27 and PCNA genes was investigated using reverse transcription polymerase chain reaction (RT-PCR). In addition, histopathology analysis of the mammary tissues was confirmed. The results revealed that DMBA treatment induced expression alterations of genes related to cancer. Also histopathological lesions were found in mammary tissues of female rats. These alterations of the gene expression as well as the histopathological lesions were markedly suppressed when female rats were treated with ENLE combined with DMBA. Conclusion: These findings suggest that ENLE exerts its anticancer properties by inhibiting alterations in the gene expression and the histopathological lesions in the mammary tissues of female rats exposed to DMBA