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Anti-cancer Activity of Two Novel Heterocyclic Compounds through Modulation of VEGFR and miRNA-122 in Mice Bearing Ehrlich Ascites Carcinoma
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  • Reem Hazem,
  • Anhar Ali,
  • Eman mahana,
  • Noha Mesbah,
  • Dina Abouelmouti,
  • Mohamed Elgawish
Reem Hazem
Suez Canal University Faculty of Pharmacy
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Anhar Ali
Sinai University - El Arish Campus
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Eman mahana
Suez Canal University Faculty of Pharmacy
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Noha Mesbah
Suez Canal University Faculty of Pharmacy
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Dina Abouelmouti
Suez Canal University Faculty of Pharmacy
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Mohamed Elgawish
Suez Canal University Faculty of Pharmacy
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Abstract

Background and Purpose: Metastasis in breast cancer is a leading cause of mortality among women in many countries. This study investigated the anti-cancer role of benzoimidazoquinazoline and benzimidazotriazin; two novel compounds that were designed, synthesized, structurally elucidated, and biologically evaluated as potent anti-angiogenic agents that act through inhibition of vascular endothelial growth factor receptor-2 (VEGFR2). A model of breast cancer was induced by inoculation of Ehrlich Ascites Carcinoma (EAC) cells. Experimental Approach: Seventy swiss albino mice were randomly divided into 7 groups, 10 animals each: (1) normal, (2) control EAC group, (3) cisplatin treated group, (4&5) benzoimidazoquinazoline treated (5mg/kg and 10mg/kg), (6&7) benzimidazotriazin treated (5mg/kg and 10 mg/kg). The expression of miRNA-122 was assessed in the tumor tissue by quantitative PCR, and the VEGF level was determined in serum by ELISA. VEGFR2 and cluster of differentiation (CD)34 were assessed by immunohistochemistry. Serum levels of ALT, AST, creatinine, and urea were measured. Key Results: Treatment with benzoimidazoquinazoline and benzimidazotriazin caused a decrease in tumor weight and a significant decrease in the serum levels of VEGF and the expression of VEGFR2 and CD34 in the tumor tissue. MiRNA-122 was significantly upregulated especially in the group treated by benzimidazotriazin (10mg/kg). Interestingly, the new compounds had less renal toxicity compared to cisplatin. Conclusion and Implication: The designed small molecules are promising anti-cancer candidates that act through inhibition of angiogenesis and can provide a new strategy for the advancement of chemotherapy through modulation of miRNA.