Uskur Tugce, Biltekin Sevde Nur, Faikoglu Gokhan, Saygisever-Faikoglu Kubra, Berk Barkın
Department of Medical Pharmacology, Faculty of Medicine, Kırklareli University, Kırklareli 39100, Türkiye.
Department of Pharmaceutical Microbiology, School of Pharmacy, Istanbul Medipol University, İstanbul 34810, Türkiye.
Pharmaceuticals (Basel). 2025 Apr 29;18(5):651. doi: 10.3390/ph18050651.
: 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. : 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. : 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. : 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.
乐卡地平是第三代二氢吡啶类钙通道阻滞剂。除了其已明确的心血管作用外，钙通道阻滞剂在各种癌症中的治疗潜力也越来越受到认可。本研究旨在通过评估细胞活力（MTT 法）、增殖、MAPK 信号通路活性、半胱天冬酶水平和 TNF-α 表达等参数，研究乐卡地平对癌细胞系的潜在抗癌作用，特别是与顺铂联合使用时的作用。
在本研究中，使用 MTT 法评估了乐卡地平单独使用以及与顺铂联合使用对 MCF-7、SH-SY5Y、PC3 和 HEK293 细胞系细胞活力的影响。为了评估细胞内信号传导和凋亡途径，使用 ELISA 检测了 MAPK 抑制以及半胱天冬酶-3 和半胱天冬酶-8 的活性。此外，为了评估抗炎潜力，通过检测脂多糖刺激的 RAW264.7 细胞中的 TNF-α 水平进行评估。
研究表明，乐卡地平显示出显著的细胞毒性作用，特别是在 SH-SY5Y 和 PC3 癌细胞系中，而在健康的 HEK293 细胞中并未诱导 50% 的活力丧失。与顺铂联合使用时，乐卡地平在神经母细胞瘤（SH-SY5Y）细胞中使细胞毒性增强了 2.7 倍，在乳腺癌（MCF7）细胞中增强了 1.6 倍，在前列腺癌（PC3）细胞中增强了 1.9 倍。在 20 μM 乐卡地平时，MAPK 活性被抑制了 83.6%，同时观察到半胱天冬酶-3 和半胱天冬酶-8 活性呈剂量依赖性增加。此外，乐卡地平降低了脂多糖刺激的 RAW264.7 细胞中的 TNF-α 水平，表明其具有潜在的抗炎作用。
总之，乐卡地平在癌细胞系中表现出选择性抗癌作用，与顺铂联合使用时显示出协同细胞毒性。它还显著抑制 MAPK 信号传导，激活凋亡半胱天冬酶，并降低 TNF-α 水平，表明其具有潜在的抗炎活性。这些发现突出了乐卡地平作为癌症治疗辅助药物重新利用的潜力。
