• Areej Salem Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Egypt, Corresponding author, E-mail:
  • Hosny Abd El-Fadil Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Egypt
  • Nagaah Al-Sayed Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Egypt
  • Ahmed S. Alazzouni Department of Zoology, Faculty of Science, Helwan University, Egypt
  • Sameh El-Nabtity Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Egypt



breast cancer, graviola, phytochemical, DMBA, 5-Flurouracil, P53, Bcl2


Breast cancer is the most frequent type of invasive cancer in women. However, chemotherapy affects all cells that grow and divide quickly in the body, including cancer and normal cells. On the other hand, Graviola is commonly used as a source of food and has a wide range of bioactive components. In this study, out of 50 albino rats, breast cancer was induced in 40 rats using 7,12-dimethylbenanthracene (DMBA). These rats were subjected to the treatment using Graviola leaves ethanolic extract (GLEE) and 5-Fluorouracil (5-FU) to evaluate the anti-carcinogenic activity and the immunohistochemical changes. A single oral dose of DMBA led to the induction of rats’ breast cancer. Induced mammary tumors were diagnosed, and all were malignant without any benign tumor. Among the malignant tumors, non-invasive, invasive, mixed (invasive and non-invasive), and unclassified malignant tumors were detected. The immunohistochemical analysis showed that estrogen and progesterone receptors revealed negative nuclear expression. However, HER2 receptors score was +3, and Ki-67 revealed 85-90% nuclear stainability, denoting a very high proliferative index. The morphometric analysis revealed that staining reactivities of HER2 and Ki-67 were 60.66 and 89.84%, respectively, and were significantly higher than ER (15.24 %) and PR (15.68%). Genetic studies revealed marked upregulation of P53 with GLEE more than 5-FU while Bcl2 showed down regulation with GLEE more than 5-FU. The quantitative analysis of GLEE phytochemical constituents showed the presence of some bioactive chemical compounds that exhibit many therapeutic activities. Therefore, GLEE improved histological appearance of DMBA induced breast cancer in female rats. Therefore, GLEE could be a promising natural alternative to chemotherapy agents as a potent anticancer.


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Veterinary Medicine and The One Health Concept