Effects of ethanol extract of curry leaves (Murraya koenigii) on HER2 and caspase-3 expression in rat model mammary carcinoma

Abstract

Background and Aim: Human epidermal growth factor receptor 2 (HER2/erbB2/neu) is a prognostic factor and biomarker for detecting mammary tumor malignancy. Leaves of curry (Murraya koenigii) contain alkaloid, flavonoid, and phenolic compounds that can be cytotoxic to tumor cells. Caspase-3 is an indicator of apoptosis in tumor cells. This study aimed to evaluate the effect of curry leaf extract on the expression of HER2 and caspase-3 in mammary tumor through immunohistochemical analyses. Materials and Methods: Thirty five Sprague-Dawley rats were divided into seven groups: negative control of tumor (P1), positive control of tumor (P2), tumor therapy with methotrexate (P3), and curry leaf extract doses of 300 and 400 mg/ kg body weight/BW after tumor formation (P4, P5), and before tumor formation (P6, P7). Thirty rats of six groups were injected subcutaneously into the mammary glands with 7,12-dimethylbenz(α)-anthracene DMBA) twice within 2 weeks for mammary tumor formation. At the end of the treatments, the rats were euthanized, and their mammary glands were analyzed histopathologically and immunohistochemically using HER2 and caspase-3 antibodies. Results: Regarding the expression of HER2 detected in the epithelial cell membrane of the mammary gland, P2, P3, P4, and P5 revealed positive expression, P6 and P7 showed equivocal expression, while P1 showed negative expression. Regarding caspase-3 expression in the cytoplasm of epithelial cells, it was low in P1, moderate in P2, P5, P6, and P7, and high in P3 and P4. These findings suggest that DMBA injection produced mammary tumors with HER2 as a biomarker of mammary tumor, and high caspase-3 expression in P4 was the effect of curry leaves extract. Conclusion: The extract of curry leaves at a dose of 300 mg/kg BW with preventive and curative effects can potentially be used as an anti-tumor agent, which effectively induces the apoptosis of tumor cells.