Novel Bradykinin Receptor Inhibitors Inhibit Proliferation and Promote the Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the ERK Pathway.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Bradykinin Receptor Antagonists/*pharmacology ; Carcinoma, Hepatocellular/*metabolism ; Cell Proliferation/*drug effects ; Liver Neoplasms/*metabolism; Bradykinin Receptor Antagonists/chemical synthesis ; Bradykinin Receptor Antagonists/chemistry ; Carcinoma, Hepatocellular/drug therapy ; Cell Line, Tumor ; Cell Survival/drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms/drug therapy ; MAP Kinase Signaling System/drug effects

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Studies have shown that bradykinin (BK) is highly expressed in liver cancer. We designed the novel BK receptor inhibitors J051-71 and J051-105, which reduced the viability of liver cancer cells and inhibited the formation of cancer cell colonies. J051-71 and J051-105 reduced cell proliferation and induced apoptosis in HepG2 and BEL-7402 cells, which may be due to the inhibition of the extracellular regulated protein kinase (ERK) signaling pathway. In addition, these BK receptor inhibitors reversed the cell proliferation induced by BK in HepG2 and BEL-7402 cells by downregulating B1 receptor expression. Inhibiting B1 receptor expression decreased the protein levels of p-ERK and reduced the malignant progression of HCC, providing a potential target for HCC therapy.

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20180101250 JC Natural Science Foundation of Jilin Province; JJKH20180178 KJ "13th Five-Year" Science and Technology Project of Jilin Provincial Department of Education

Keywords: ERK signaling pathway; apoptosis; bradykinin B1 receptor; bradykinin receptor inhibitor; hepatocellular carcinoma

0 (Antineoplastic Agents)
0 (Bradykinin Receptor Antagonists)
EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)

Date Created: 20210702 Date Completed: 20210721 Latest Revision: 20210721

20231215

PMC8272207

10.3390/molecules26133915

34206871