Research Article

Enhanced Anticancer Effect of Temozolomide through Synergistic Combination with Diltiazem in Neuroblastoma (SH-SY5Y) Cell Line

Volume: 45 Number: 2 June 30, 2023
EN

Enhanced Anticancer Effect of Temozolomide through Synergistic Combination with Diltiazem in Neuroblastoma (SH-SY5Y) Cell Line

Abstract

Objective: This study aimed to assess the enhanced anticancer effect of Temozolomide (TMZ) through a synergistic combination with Diltiazem (DTZ) in the neuroblastoma cell line (SH-SY5Y). Material and Methods: The SH-SY5Y neuroblastoma cell line was cultured in a DMEM medium. TMZ and DTZ stock solutions were prepared and diluted to obtain different concentrations. The XTT assay was performed to evaluate cell viability. Cells were treated with TMZ alone or with DTZ for 24 and 48 hours. Viability was measured using the XTT-formazan product, and statistical analysis was performed. Results: The viability of neuroblastoma cells treated with TMZ alone and TMZ+DTZ combination was assessed. At 24 hours, TMZ showed no cytotoxic effect, while DTZ showed a low cytotoxic impact. At 48 hours, TMZ and TMZ+DTZ combination exhibited significant cytotoxic effects. The cytotoxic effects were concentration-dependent and time-dependent. DTZ alone showed significant cytotoxic effects on neuroblastoma cells at specific concentrations. Conclusion: The study demonstrated that TMZ alone and combined with DTZ had a significant cytotoxic effect on neuroblastoma cells. The combination of TMZ and DTZ may enhance the anticancer effect of TMZ and overcome drug resistance in neuroblastoma treatment. DTZ, a P-glycoprotein inhibitor, could prevent the efflux of TMZ from cancer cells, increasing its concentration and effectiveness.

Keywords

References

  1. 1. Li Y, Nakagawara A. Apoptotic Cell Death in Neuroblastoma. Cells. 2013;2(2):432–59. 2. Friedman HS, Kerby T, Calvert H. Temozolomide and treatment of malignant glioma. Clin Cancer Res. 2000;6(7):2585–97.
  2. 3. Karthika C, Sureshkumar R, Zehravi M, Akter R, Ali F, Ramproshad S, et al. Multidrug Resistance of Cancer Cells and the Vital Role of P‐Glycoprotein. Life. 2022;12(6):1–20.
  3. 4. Urquhart BL, Kim RB. Blood-brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol. 2009;Nov;65(11):1063–70. htps://pubmed.ncbi.nlm.nih.gov/19727692/
  4. 5. Barnett-Griness O, Rennert G, Lejbkowicz F, Pinchev M, Saliba W, Gronich N. Association Between ABCG2, ABCB1, ABCC2 Efflux Transporter Single-Nucleotide Variants and Irinotecan Adverse Effects in Patients With Colorectal Cancer: A Real-Life Study. Clin Pharmacol Ther.2023; Mar;113(3):704–11.https://onlinelibrary.wiley.com/doi/full/10.1002/cpt.2833.
  5. 6. Shah D, Ajazuddin, Bhattacharya S. Role of natural P-gp inhibitor in effectively delivering chemotherapeutic agents. J Cancer Res Clin Oncol. 2023 Jan. 9;149(1):367–91. https://link.springer.com/article/10.1007/s00432-022-04387-2.
  6. 7. Keyel ME, Reynolds CP. Spotlight on dinutuximab in treating high-risk neuroblastoma: Development and place in therapy. Biol Targets Ther. 2019;13:1–12.
  7. 8. Pylayeva-Gupta Y, Kelsey C. Martin Mhatre V. Ho J-AL. STIM Is a Ca2+ Sensor Essential for Ca2+-Store-DepletionTriggered Ca2+ Influx. Bone. 2012;23(1):1–7.
  8. 9. Basile J. The Role of Existing and Newer Calcium Channel Blockers in the Treatment of Hypertension. J Clin Hypertens. 2004 Nov.;6(11):621–9. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1524-6175.2004.03683.x

Details

Primary Language

English

Subjects

Health Systems

Journal Section

Research Article

Early Pub Date

June 30, 2023

Publication Date

June 30, 2023

Submission Date

June 12, 2023

Acceptance Date

June 23, 2023

Published in Issue

Year 2023 Volume: 45 Number: 2

AMA
1.Karademir M, Surardamar S. Enhanced Anticancer Effect of Temozolomide through Synergistic Combination with Diltiazem in Neuroblastoma (SH-SY5Y) Cell Line. CMJ. 2023;45(2):46-51. doi:10.7197/cmj.1313269