International Journal of Materials Science and Applications

Submit a Manuscript

Publishing with us to make your research visible to the widest possible audience.

Propose a Special Issue

Building a community of authors and readers to discuss the latest research and develop new ideas.

Cytotoxic and Apoptotic Effects of Simvastatin on Human Dental Pulp Cells

Statins, specifically hydroxymethylglutaryl-coenzyme-A reductase inhibitors (HMG-Co-A), are well-recognized for their capacity to reduce plasma cholesterol levels. Nevertheless, a comprehensive investigation into the biocompatibility of Simvastatin with human dental pulp cells has been somewhat lacking. The principal objective of this study was to conduct an in-depth examination of the effects of varying concentrations of Simvastatin on critical aspects such as cell attachment, proliferation, toxicity, cell cycle progression, and apoptosis in normal human dental pulp cells. To execute this, dental pulp cells derived from healthy human pulp tissue were subjected to Simvastatin treatments at concentrations ranging from 1 µmol/L to 100 µmol/L, with a control group at 0 µmol/L. The evaluation encompassed an assessment of cell attachment at a 16-hour interval. Subsequent investigations spanned proliferation rates and cytotoxicity assessments conducted at 7, 14, and 21 days. Additional analyses included cell cycle progression and apoptotic events at 1- and 3 days post-treatment. The statistical analysis relied on ANOVA, with a significance threshold set at p-values of ≤0.05. The results yielded several noteworthy findings. Notably, a concentration of 25 µmol/L demonstrated a substantial and statistically significant enhancement (p < 0.001) in cell attachment efficiency. However, it became evident that all tested concentrations of Simvastatin led to a marked reduction in the proliferation rate (p < 0.001) and a concurrent increase in cytotoxicity (p < 0.001). Furthermore, the analysis of cell cycle progression and apoptosis revealed a progressive and statistically significant increase with the passage of time (p < 0.001). In summary, the outcomes of this investigation underscore a prominent adverse effect of Simvastatin on normal human dental pulp cells. Specifically, this statin appears to detrimentally influence cell proliferation and overall cell viability through the induction of apoptosis, as indicated by the findings of this study.

Simvastatin, Human Dental Pulp Cells, Toxicity, Apoptosis

Kanwal Maheshwari, Vijay Maheshwari, Laisheng Chou. (2023). Cytotoxic and Apoptotic Effects of Simvastatin on Human Dental Pulp Cells. International Journal of Materials Science and Applications, 12(5), 59-66.

Copyright © 2023 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Corsini A, Bellosta S, Baetta R, Fumagalli R, Paoletti R, Bernini F. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther 1999; 84 (3): 413-428.
2. Abeles AM, Pillinger MH. Statins as antiinflammatory and immunomodulatory agents: a future in rheumatologic therapy? Arthritis Rheum 2006; 54 (2): 393-407.
3. Kwak B, Mulhaupt F, Veillard N, Pelli G, Mach F. The HMG-CoA reductase inhibitor simvastatin inhibits IFN-gamma induced MHC class II expression in human vascular endothelial cells. Swiss Med Wkly 2001; 131 (3-4): 41-46.
4. Vollmer T, Key L, Durkalski V, Tyor W, Corboy J, Markovic-Plese S, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 2004; 363 (9421): 1607-1608.
5. Hatzigeorgiou C, Jackson JL. Hydroxymethylglutaryl-coenzyme A reductase inhibitors and osteoporosis: a meta-analysis. Osteoporos Int 2005; 16 (8): 990-998.
6. Okamoto Y, Sonoyama W, Ono M, Akiyama K, Fujisawa T, Oshima M, et al. Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo. J Endod 2009; 35 (3): 367-372.
7. Samiei M, Aghazadeh M, Alizadeh E, Aslaminabadi N, Davaran S, Shirazi S, et al. Osteogenic/Odontogenic Bioengineering with co-Administration of Simvastatin and Hydroxyapatite on Poly Caprolactone Based Nanofibrous Scaffold. Adv Pharm Bull 2016; 6 (3): 353-365.
8. Jia W, Zhao Y, Yang J, Wang W, Wang X, Ling L, et al. Simvastatin Promotes Dental Pulp Stem Cell-induced Coronal Pulp Regeneration in Pulpotomized Teeth. J Endod 2016; 42 (7): 1049-1054.
9. Varalakshmi PR, Kavitha M, Govindan R, Narasimhan S. Effect of statins with alpha-tricalcium phosphate on proliferation, differentiation, and mineralization of human dental pulp cells. J Endod 2013; 39 (6): 806-812.
10. Lin SK, Kok SH, Lee YL, Hou KL, Lin YT, Chen MH, et al. Simvastatin as a novel strategy to alleviate periapical lesions. J Endod 2009; 35 (5): 657-662.
11. Lee SY, Min KS, Choi GW, Park JH, Park SH, Lee SI, et al. Effects of simvastain and enamel matrix derivative on Portland cement with bismuth oxide-induced growth and odontoblastic differentiation in human dental pulp cells. J Endod 2012; 38 (3): 405-410.
12. Jung JY, Woo SM, Kim WJ, Lee BN, Nor JE, Min KS, et al. Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells. Int Endod J 2017; 50 (4): 377-386.
13. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences 2000; 97 (25): 13625-13630.
14. Hilkens P, Gervois P, Fanton Y, Vanormelingen J, Martens W, Struys T, et al. Effect of isolation methodology on stem cell properties and multilineage differentiation potential of human dental pulp stem cells. Cell and tissue research 2013; 353 (1): 65-78.
15. Raoof M, Yaghoobi MM, Derakhshani A, Kamal-Abadi AM, Ebrahimi B, Abbasnejad M, et al. A modified efficient method for dental pulp stem cell isolation. Dental Research Journal 2014; 11 (2): 244.
16. Lai EH, Hong CY, Kok SH, Hou KL, Chao LH, Lin LD, et al. Simvastatin alleviates the progression of periapical lesions by modulating autophagy and apoptosis in osteoblasts. J Endod 2012; 38 (6): 757-763.
17. Lin LD, Lin SK, Chao YL, Kok SH, Hong CY, Hou KL, et al. Simvastatin suppresses osteoblastic expression of Cyr61 and progression of apical periodontitis through enhancement of the transcription factor Forkhead/winged helix box protein O3a. J Endod 2013; 39 (5): 619-625.
18. Min KS, Lee YM, Hong SO, Kim EC. Simvastatin promotes odontoblastic differentiation and expression of angiogenic factors via heme oxygenase-1 in primary cultured human dental pulp cells. J Endod 2010; 36 (3): 447-452.
19. Karanxha L, Park SJ, Son WJ, Nor JE, Min KS. Combined effects of simvastatin and enamel matrix derivative on odontoblastic differentiation of human dental pulp cells. J Endod 2013; 39 (1): 76-82.
20. Yazawa H, Zimmermann B, Asami Y, Bernimoulin JP. Simvastatin promotes cell metabolism, proliferation, and osteoblastic differentiation in human periodontal ligament cells. J Periodontol 2005; 76 (2): 295-302.
21. Liu C, Wu Z, Sun HC. The effect of simvastatin on mRNA expression of transforming growth factor-beta1, bone morphogenetic protein-2 and vascular endothelial growth factor in tooth extraction socket. Int J Oral Sci 2009; 1 (2): 90-98.
22. Baek KH, Lee WY, Oh KW, Tae HJ, Lee JM, Lee EJ, et al. The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells. Journal of Korean medical science 2005; 20 (3): 438-444.
23. Saewong S, Thammasitboon K, Wattanaroonwong N. Simvastatin induces apoptosis and disruption of the actin cytoskeleton in human dental pulp cells and periodontal ligament fibroblasts. Archives of oral biology 2013; 58 (8): 964-974.
24. Bardou M, Barkun A, Martel M. Effect of statin therapy on colorectal cancer. Gut 2010; 59 (11): 1572-1585.