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Research Article
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Year 2023, Volume: 45 Issue: 2, 46 - 51, 30.06.2023

Mustafa Karademir , Saime Surardamar

https://doi.org/10.7197/cmj.1313269

Abstract

References

  • 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.
  • 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.
  • 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/
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 10. Pingili RB, Mullapudi SS, Vemulapalli S, Kilaru NB. Influence of hesperetin on the pharmacokinetics of Diltiazem in rats. J Appl Pharm Sci. 2023 Jan. https://japsonline.com/abstract.php?article_id=3911&sts=2
  • 11. Xu Y, Shen M, Li Y, Sun Y, Teng Y, Wang Y, et al. The synergic antitumor effects of paclitaxel and Temozolomide co-loaded in mPEG-PLGA nanoparticles on glioblastoma cells. Oncotarget 2016 Apr.;7(15):20890. /PMC/articles/PMC4991499/
  • 12. Cornwell MM, Pastan I, Gottesman MM. Certain calcium channel blockers bind specifically to multidrug-resistant human KB carcinoma membrane vesicles and inhibit drug binding to P-glycoprotein. J.Biol Chem.1987;262(5):2166–70. http://dx.doi.org/10.1016/S0021-9258(18)61633-3
  • 13. Summers MA, Moore JL, McAuley JW. Use of verapamil as a potential P-glycoprotein inhibitor in a patient with refractory epilepsy. Ann Pharmacother. 2004,Oct.,38(10):1631–4. https://pubmed.ncbi.nlm.nih.gov/15328394/
  • 14. El-Mahdy HA, El-Husseiny AA, Kandil YI, Gamal El-Din AM. Diltiazem potentiates the cytotoxicity of gemcitabine and 5-fluorouracil in PANC-1 human pancreatic cancer cells by inhibiting P-glycoprotein. Life Sci.2020, Dec;262. https://pubmed.ncbi.nlm.nih.gov/33011221/
  • 15. Ahmed Juvale II, Abdul Hamid AA, Abd Halim KB, Che Has AT. P-glycoprotein: new insights into the structure, physiological function, regulation and alterations in disease. Heliyon. 2022 Jun;8(6). PMC/articles/PMC9249865/
  • 16. Juan-Carlos PDM, Perla-Lidia PP, Stephanie-Talia MM, Mónica-Griselda AM, Luz-María TE. ABC transporter superfamily. An updated overview, relevance in cancer multidrug resistance and perspectives with personalized medicine. Mol Biol Rep. 2021,Feb;48(2):1883–901. https://pubmed.ncbi.nlm.nih.gov/33616835/
  • 17. Karthikeyan S, Hoti S. Development of Fourth Generation ABC Inhibitors from Natural Products: A Novel Approach to Overcome Cancer Multidrug Resistance. Anticancer Agents Med Chem. 2015;15(5):605–15.

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

Year 2023, Volume: 45 Issue: 2, 46 - 51, 30.06.2023

Mustafa Karademir , Saime Surardamar

https://doi.org/10.7197/cmj.1313269

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

Temozolamide Diltiazem Neuroblastoma, P-Gp Drug resistance Cytotoxity

References

  • 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.
  • 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.
  • 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/
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 10. Pingili RB, Mullapudi SS, Vemulapalli S, Kilaru NB. Influence of hesperetin on the pharmacokinetics of Diltiazem in rats. J Appl Pharm Sci. 2023 Jan. https://japsonline.com/abstract.php?article_id=3911&sts=2
  • 11. Xu Y, Shen M, Li Y, Sun Y, Teng Y, Wang Y, et al. The synergic antitumor effects of paclitaxel and Temozolomide co-loaded in mPEG-PLGA nanoparticles on glioblastoma cells. Oncotarget 2016 Apr.;7(15):20890. /PMC/articles/PMC4991499/
  • 12. Cornwell MM, Pastan I, Gottesman MM. Certain calcium channel blockers bind specifically to multidrug-resistant human KB carcinoma membrane vesicles and inhibit drug binding to P-glycoprotein. J.Biol Chem.1987;262(5):2166–70. http://dx.doi.org/10.1016/S0021-9258(18)61633-3
  • 13. Summers MA, Moore JL, McAuley JW. Use of verapamil as a potential P-glycoprotein inhibitor in a patient with refractory epilepsy. Ann Pharmacother. 2004,Oct.,38(10):1631–4. https://pubmed.ncbi.nlm.nih.gov/15328394/
  • 14. El-Mahdy HA, El-Husseiny AA, Kandil YI, Gamal El-Din AM. Diltiazem potentiates the cytotoxicity of gemcitabine and 5-fluorouracil in PANC-1 human pancreatic cancer cells by inhibiting P-glycoprotein. Life Sci.2020, Dec;262. https://pubmed.ncbi.nlm.nih.gov/33011221/
  • 15. Ahmed Juvale II, Abdul Hamid AA, Abd Halim KB, Che Has AT. P-glycoprotein: new insights into the structure, physiological function, regulation and alterations in disease. Heliyon. 2022 Jun;8(6). PMC/articles/PMC9249865/
  • 16. Juan-Carlos PDM, Perla-Lidia PP, Stephanie-Talia MM, Mónica-Griselda AM, Luz-María TE. ABC transporter superfamily. An updated overview, relevance in cancer multidrug resistance and perspectives with personalized medicine. Mol Biol Rep. 2021,Feb;48(2):1883–901. https://pubmed.ncbi.nlm.nih.gov/33616835/
  • 17. Karthikeyan S, Hoti S. Development of Fourth Generation ABC Inhibitors from Natural Products: A Novel Approach to Overcome Cancer Multidrug Resistance. Anticancer Agents Med Chem. 2015;15(5):605–15.
There are 16 citations in total.

Details

Primary Language English
Subjects Health Systems
Journal Section Surgical Science Research Articles
Authors

Mustafa Karademir 0000-0002-0734-9040

Saime Surardamar 0000-0002-2052-8836

Early Pub Date June 30, 2023
Publication Date June 30, 2023
Acceptance Date June 23, 2023
Published in Issue Year 2023 Volume: 45 Issue: 2

Cite

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