Abstract
Background: Metastasis represents an advanced stage of cancers, and matrix metalloproteinases are critical regulators. Calcium signal is crucial for appropriate cell behaviors. The efficacy and effects of calcium channel blockers in treating cancers are individually differ from each other. Here, we attempt to investigate the effects of nicardipine, a FDA-approved calcium channel blocker, in advanced breast cancers.Methods: We analyzed the influence of nicardipine on the colony-forming ability of triple negative breast cancer cell lines. Using cell culture inserts, cell migration was also examined. The expression of regulatory proteins was evaluated by real-time PCR, Western blot, and ELISA.Results: We have confirmed that nicardipine inhibits the breast cancer cells migration and colony formation. In addition, we also revealed that nicardipine increases the Nrf2 and HO-1 expression. The inhibition of HO-1 abrogates nicardipine-reduced matrix metalloproteinase-9 expression. Moreover, the end products of HO-1, namely, CO, Fe2+, and biliverdin (will converted to bilirubin), also decreases the expression of matrix metalloproteinase-9.Conclusion: These findings suggest that nicardipine-mediated matrix metalloproteinase-9 reduction is regulated by Nrf2/HO-1 axis and its catalytic end products. Therefore, nicardipine may be a potential candidate for repurposing against advanced breast cancers.
Highlights
Metastasis is a multistep process representing an advanced stage of malignancy and is the leading cause of cancer-related deaths
Since nicardipine was reconstituted with DMSO, cells of the control group were treated with 0.1% DMSO as vehicle control
matrix metalloproteinases (MMP)-9 activity was reduced to 0.48 ± 0.04-fold of control at the highest dosage treated on MDA-MB-231 cells. These results indicated that nicardipine significantly reduced the MMP-9 expression and activity in breast cancer cells
Summary
Metastasis is a multistep process representing an advanced stage of malignancy and is the leading cause of cancer-related deaths. One key aspect of metastasis is the invasiveness of the cancer cells, which is mainly driven by cell motility and colony formation (Tahtamouni et al, 2019). These processes require the involvement of a wide array of molecular alterations such as the expression of proteolytic enzymes (Novikov et al, 2021). Metastasis represents an advanced stage of cancers, and matrix metalloproteinases are critical regulators. The efficacy and effects of calcium channel blockers in treating cancers are individually differ from each other. We attempt to investigate the effects of nicardipine, a FDA-approved calcium channel blocker, in advanced breast cancers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
