Newly Synthesized Benzimidazoles Inhibit Vascular Endothelial Growth Factor and Matrix Metalloproteinase-2 and-9 Levels in Prostate Cancer Cells
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2022
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Abstract
Background: Investigating the effects of newly synthesized agents on various molecular mechanisms to understand their mechanism of action is an important step of pre-clinical screening. Benzimidazoles are composed of a unique fused benzene and imidazole ring and have attracted great attention due to their broad bioactivities, including antitumor. Objective: In the current study, we reported the synthesis of novel benzimidazole derivatives and investigated the pos-sible cytotoxic and anti-angiogenic effects on human prostate cancer and umbilical vein endothelial cells (HUVECs). Methods: MTT assay was used to assess cell viability. A scratch assay was conducted to monitor the migration of cells. mRNA expression levels of VEGF, MMP-2, and MMP-9 were evaluated using qPCR. Changes in protein levels were evaluated by western blotting. Results: Compound G1, having a chlorine moiety, showed a potent cytotoxic activity on both prostate cancer cells and HUVECs, and inhibited cell migration via decreasing the mRNA and protein levels of key angiogenesis-related molecules such as VEGF, MMP-2, and MMP-9. Conclusion: These results suggest that newly synthesized G1 may be a novel anti-angiogenic agent for prostate cancer treatment. © 2022 Bentham Science Publishers.
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Angiogenesis Inhibitors , Antineoplastic Agents , Benzimidazoles , Cell Movement , Human Umbilical Vein Endothelial Cells , Humans , Male , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Prostatic Neoplasms , RNA, Messenger , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors , 2 bromopropane , 2 propanol , acetic acid ethyl ester , acetone , benzimidazole , beta actin , chlorine , complementary DNA , dimethyl sulfoxide , fluorouracil , formaldehyde , gelatinase A , gelatinase B , glutamine , messenger RNA , penicillin derivative , piperidine , SYBR green , vasculotropin , angiogenesis inhibitor , antineoplastic agent , benzimidazole derivative , gelatinase A , gelatinase B , messenger RNA , vasculotropin , vasculotropin A , agar gel electrophoresis , angiogenesis , antiangiogenic activity , Article , Bradford assay , cell migration , cell viability , crystallization , cytotoxicity , drug synthesis , DU145 cell line , fetal bovine serum , human , human cell , HUVEC cell line , IC50 , liquid chromatography-mass spectrometry , microscopy , mRNA expression level , MTT assay , PC-3 [Human prostate carcinoma] cell line , polyacrylamide gel electrophoresis , prostate cancer , prostate cancer cell line , proton nuclear magnetic resonance , quantitative analysis , real time polymerase chain reaction , RNA isolation , room temperature , spectroscopy , umbilical vein endothelial cell , Western blotting , wound healing assay , cell motion , genetics , male , metabolism , prostate tumor , umbilical vein endothelial cell