Protective effects of hesperidin through attenuation of Ki67 expression against DMBA-induced breast cancer in female rats

Abstract

Aims: Doxorubicin (Dox) is routinely used for breast cancer treatment but toxicity and drug resistance limit its use. The objective of the study was to investigate the protective effects of hesperidin alone and in combination with doxorubicin against experimentally induced breast cancer in female rats. Methods: Breast cancer (BC) was induced by administration of 7,12-dimethylbenz(a)anthracene (DMBA) through subcutaneous injection into the 3rd right mammary gland of female Wistar rats. Hesperidin (Hes) pretreated groups were started with Hes (200 mg/kg) two weeks prior to DMBA induction. Animals were randomly divided into nine groups namely vehicle control, DMBA-induced, Dox 4 mg/kg, Dox 2 mg/kg, Hes (200 mg/kg), Hes (200 mg/kg) plus Dox 4 mg/kg treated groups and Hes pretreated groups treated with DMBA, Dox 4 mg/kg and Dox 2 mg/kg. Key findings: Hes pretreated groups showed reduced tumor occurrence, tumor volume and increased survival rate as compared to DMBA-induced group of animals. Hes pretreated animals treated with Dox 4 mg/kg and 2 mg/kg exhibited significant reduction in malondialdehyde and improvement in levels of glutathione and inflammatory markers like IL-6, TNF-α, NF-κB, IFN-γ as compared to Dox 4 mg/kg and 2 mg/kg treated animals. Histopathology and Ki67 expression depicted better control of tumor with Hes pretreatment groups as compared to DMBA-induced. Histopathology of vital organs of Hes pretreated groups treated with Dox revealed lesser toxicity than Dox treated groups. Significance: Hesperidin possesses protective effect against experimentally induced breast cancer in female rats that appears to be related to attenuation of Ki67 expression.