# Lercanidipine Enhances Cisplatin Activity: Dual Anticancer and Anti-Inflammatory Effects via Caspase Activation and MAPK Inhibition

## TL;DR

Lercanidipine, a calcium channel blocker, enhances cisplatin's anticancer effects by boosting cell death and reducing inflammation in cancer cells.

## Contribution

The study demonstrates lercanidipine's dual anticancer and anti-inflammatory effects via caspase activation and MAPK inhibition when combined with cisplatin.

## Key findings

- Lercanidipine showed significant cytotoxicity in SH-SY5Y and PC3 cancer cells without harming healthy HEK293 cells.
- Combining lercanidipine with cisplatin increased cytotoxicity by up to 2.7-fold in neuroblastoma cells.
- Lercanidipine inhibited MAPK activity by 83.6% and reduced TNF-α levels in inflammatory cells.

## Abstract

Background/Objectives: Lercanidipine is a third-generation dihydropyridine calcium channel blocker. In addition to their well-established cardiovascular effects, calcium channel blockers are increasingly recognized for their therapeutic potential in various cancers. This study aimed to investigate the potential anticancer effects of lercanidipine on cancer cell lines—particularly in combination with cisplatin—by assessing parameters such as cell viability (MTT assay), proliferation, MAPK pathway activity, caspase enzyme levels, and TNF-α expression. Methods: In this study, the effects of lercanidipine, both alone and in combination with cisplatin, on cell viability were evaluated using the MTT assay in MCF-7, SH-SY5Y, PC3, and HEK293 cell lines. To assess intracellular signaling and apoptotic pathways, MAPK inhibition, as well as caspase-3 and caspase-8 activities, were measured using ELISA. Additionally, to evaluate the anti-inflammatory potential, TNF-α levels in LPS-stimulated RAW264.7 cells were analyzed via. Results: The study revealed that lercanidipine showed significant cytotoxic effects, particularly in SH-SY5Y and PC3 cancer cell lines, while it did not induce a 50% loss of viability in healthy HEK293 cells. When combined with cisplatin, lercanidipine enhanced cytotoxicity by 2.7-fold in neuroblastoma (SH-SY5Y) cells, 1.6-fold in breast cancer (MCF7) cells, and 1.9-fold in prostate cancer (PC3) cells. MAPK activity was inhibited by 83.6% at 20 μM lercanidipine, while dose-dependent increases in caspase-3 and caspase-8 activities were observed. Additionally, lercanidipine decreased TNF-α levels in LPS-stimulated RAW264.7 cells, indicating its potential anti-inflammatory effect. Conclusions: In conclusion, lercanidipine demonstrated selective anticancer effects in cancer cell lines and showed synergistic cytotoxicity when combined with cisplatin. It also significantly inhibited MAPK signaling, activated apoptotic caspases, and reduced TNF-α levels, suggesting potential anti-inflammatory activity. These findings highlight lercanidipine’s potential for repurposing as an adjunct in cancer therapy.