دوشنبه 26 مرداد 1405
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Introduction: Dihydropyridine (DHP) calcium channel blockers have shown anticancer-related effects in preclinical studies, but the cytotoxic activity of the novel 1,4-DHP derivatives mebudipine and dibudipine in melanoma remains unclear. This study compared the in vitro cytotoxicities of mebudipine, dibudipine, and dacarbazine in B16-F10 melanoma cells and in HEK293 comparative nonmelanoma cells.
Materials and Methods: B16-F10 and HEK293 cells were treated with mebudipine, dibudipine, or dacarbazine for 24 and 48 hours. Cell viability was measured via the MTT assay. Concentration‒response curves were fitted by nonlinear regression, and the IC₅₀ values were reported with 95% confidence intervals.
Results: After 24h, B16-F10 cells presented the lowest IC₅₀ for mebudipine [13.51 µg/mL; 95% CI, 8.86–20.45], followed by dacarbazine [33.47 µg/mL; 95% CI, 22.24–49.57] and dibudipine [59.13 µg/mL; 95% CI, 25.62–128.90; P=0.0006]. In HEK293 cells, the preferred shared IC₅₀ at 24h was 159.9 µg/mL (95% CI, 120.6–217.9; P=0.3618). After 48h, B16-F10 cells remained highly sensitive to mebudipine [9.738 µg/mL; 95% CI, 6.673–14.29] and dacarbazine [9.749 µg/mL; 95% CI, 6.627–14.42], whereas dibudipine was less potent [30.96 µg/mL; 95% CI, 15.19–57.85; P=0.0025]. In HEK293 cells at 48h, the IC₅₀ values were 90.40, 206.5, and 74.66 µg/mL for mebudipine, dibudipine, and dacarbazine, respectively (P=0.0063).
Conclusion: Mebudipine showed stronger cytotoxic activity against B16-F10 cells than dibudipine at both time points, with higher IC₅₀ values in HEK293 cells. Since HEK293 cells are transformed, these data indicate comparative cytotoxicity rather than confirmed safety in normal cells. Further mechanistic melanoma studies are warranted.
Materials and Methods: B16-F10 and HEK293 cells were treated with mebudipine, dibudipine, or dacarbazine for 24 and 48 hours. Cell viability was measured via the MTT assay. Concentration‒response curves were fitted by nonlinear regression, and the IC₅₀ values were reported with 95% confidence intervals.
Results: After 24h, B16-F10 cells presented the lowest IC₅₀ for mebudipine [13.51 µg/mL; 95% CI, 8.86–20.45], followed by dacarbazine [33.47 µg/mL; 95% CI, 22.24–49.57] and dibudipine [59.13 µg/mL; 95% CI, 25.62–128.90; P=0.0006]. In HEK293 cells, the preferred shared IC₅₀ at 24h was 159.9 µg/mL (95% CI, 120.6–217.9; P=0.3618). After 48h, B16-F10 cells remained highly sensitive to mebudipine [9.738 µg/mL; 95% CI, 6.673–14.29] and dacarbazine [9.749 µg/mL; 95% CI, 6.627–14.42], whereas dibudipine was less potent [30.96 µg/mL; 95% CI, 15.19–57.85; P=0.0025]. In HEK293 cells at 48h, the IC₅₀ values were 90.40, 206.5, and 74.66 µg/mL for mebudipine, dibudipine, and dacarbazine, respectively (P=0.0063).
Conclusion: Mebudipine showed stronger cytotoxic activity against B16-F10 cells than dibudipine at both time points, with higher IC₅₀ values in HEK293 cells. Since HEK293 cells are transformed, these data indicate comparative cytotoxicity rather than confirmed safety in normal cells. Further mechanistic melanoma studies are warranted.
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