Disulfiram-Loaded Niosomes Reduces Cancerous Phenotypes in Oral Squamous Cell Carcinoma Cells

Document Type : Original Article

Authors

1 Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran

2 Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Pathology, Cancer Institute Hospital, IKHC, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

5 Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden

Abstract

Objective: Surgery and chemotherapy are the most common therapeutic strategies proposed for oral squamous cell
carcinoma (OSCC). However, some of the disadvantages associated with the current methods like unwanted side
effects and poor drug response lead the scientist to seek for novel modalities and delivery approaches to enhance the
efficacy of treatments. The study aimed to assess the effectiveness of disulfiram (DSF)-loaded Niosomes on cancerous
phenotypes of the OSCC cells.
Materials and Methods: In this experimental study, an optimum formulation of DSF-loaded Niosomes was developed
for the treatment of OSCC cells to reduce drug doses and improve the poor stability of DSF in the OSCC environment.
The design expert software was utilized to optimize the particles in terms of size, polydispersity index (PDI), and
entrapment effcacy (EE).

Results: Acidic pH increased the release rate of DSF from these formulations. The size, PDI, and EE of Niosomes
were more stable at 4°C compared to 25°C. The results indicated that DSF-loaded Niosomes could induce apoptosis
(P=0.019) in the OSCC cells compared to the control group. Moreover, it could reduce colony formation ability
(P=0.0046) and also migration capacity of OSCC cells (P=0.0015).

Conclusion: Our findings indicated that the application of proper dose of DSF-loaded Niosomes (12.5 μg/ml) increases
apoptosis, decreases colony formation capacity and declines the migration ability of OSCC cells.

Keywords

Main Subjects

References

  1. Nagao T, Warnakulasuriya S. Screening for oral cancer: future prospects, research and policy development for Asia. Oral Oncol. 2020; 105: 104632.
  2. Cristaldi M, Mauceri R, Di Fede O, Giuliana G, Campisi G, Panzarella V. Salivary biomarkers for oral squamous cell carcinoma diagnosis and follow-up: current status and perspectives. Front Physiol. 2019; 10: 1476.
  3. Fazli B, Irani S, Bardania H, Moosavi MS, Rohani B. Prophylactic effect of topical (slow-release) and systemic curcumin nanoniosome antioxidant on oral cancer in rat. BMC Complement Med Ther. 2022; 22(1): 109.
  4. Bugshan A, Farooq I. Oral squamous cell carcinoma: metastasis, potentially associated malignant disorders, etiology and recent advancements in diagnosis. F1000Res. 2020; 9: 229.
  5. Liu L, Chen J, Cai X, Yao Z, Huang J. Progress in targeted therapeutic drugs for oral squamous cell carcinoma. Surg Oncol. 2019; 31: 90-97.
  6. Farooq MA, Aquib M, Khan DH, Hussain Z, Ahsan A, Baig MMFA, et al. Recent advances in the delivery of disulfiram: a critical analysis of promising approaches to improve its pharmacokinetic profile and anticancer efficacy. Daru. 2019; 27(2): 853-862.
  7. Yeung KT, Yang J. Epithelial-mesenchymal transition in tumor metastasis. Mol Oncol. 2017; 11(1): 28-39.
  8. Bu W, Wang Z, Meng L, Li X, Liu X, Chen Y, et al. Disulfiram inhibits epithelial-mesenchymal transition through TGFβ-ERK-Snail pathway independently of Smad4 to decrease oral squamous cell carcinoma metastasis. Cancer Manag Res. 2019; 11: 3887-3898.
  9. Rezaei N, Akbarzadeh I, Kazemi S, Montazeri L, Zarkesh I, Hossein- Khannazer N, et al. Smart materials in regenerative medicine. Mod Med Lab J. 2021; 4(1): 39-51.
  10. Akbarzadeh I, Farid M, Javidfar M, Zabet N, Shokoohian B, Arki MK, et al. The optimized formulation of tamoxifen-loaded niosomes efficiently induced apoptosis and cell cycle arrest in breast cancer cells. AAPS PharmSciTech. 2022; 23(1): 57.
  11. Akbarzadeh I, Fatemizadeh M, Heidari F, Niri NM. Niosomal formulation for co-administration of hydrophobic anticancer drugs into MCF-7 cancer cells. Arch Adv Biosci. 2020; 11(2): 1-9.
  12. Bartelds R, Nematollahi MH, Pols T, Stuart MCA, Pardakhty A, Asadikaram G, et al. Niosomes, an alternative for liposomal delivery. PLoS One. 2018; 13(4): e0194179.
  13. Rezaei N, Kazem Arki M, Miri-Lavasani Z, Solhi R, Khoramipour M, Rashedi H, et al. Co-delivery of doxorubicin and paclitaxel via noisome nanocarriers attenuates cancerous phenotypes in gastric cancer cells. Eur J Pharm Biopharm. 2023: S0939-6411(23)00102- 9.
  14. Rochani AK, Balasubramanian S, Ravindran Girija A, Raveendran S, Borah A, Nagaoka Y, et al. Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation. Int J Pharm. 2016; 511(1): 648-658.
  15. Alemi A, Zavar Reza J, Haghiralsadat F, Zarei Jaliani H, Haghi Karamallah M, Hosseini SA, et al. Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy. J Nanobiotechnology. 2018; 16(1): 28.
  16. Jaya Prakash N, Shanmugarajan D, Kandasubramanian B, Khot P, Kodam K. Biodegradable silk-curcumin composite for sustained drug release and visual wound monitoring. Mater Today Chem. 2023; 27: 101289.
  17. Karimifard S, Rezaei N, Jamshidifar E, Moradi Falah Langeroodi S, Abdihaji M, Mansouri A, et al. PH-responsive chitosan-adorned niosome nanocarriers for co-delivery of drugs for breast cancer therapy. ACS Appl Nano Mater. 2022; 5(7): 8811-8825.
  18. Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc. 2006; 1(5): 2315- 2319.
  19. Pourtalebi Jahromi L, Ghazali M, Ashrafi H, Azadi A. A comparison of models for the analysis of the kinetics of drug release from PLGA-based nanoparticles. Heliyon. 2020; 6(2): e03451.
  20. Heredia NS, Vizuete K, Flores-Calero M, Pazmiño VK, Pilaquinga F, Kumar B, et al. A. Comparative statistical analysis of the release kinetics models for nanoprecipitated drug delivery systems based on poly(lactic-co-glycolic acid). PLoS One. 2022; 17(3): e0264825.
  21. Sadeghi S, Ehsani P, Ahangari Cohan R, Sardari S, Akbarzadeh I, Bakhshandeh H, et al. Design and physicochemical characterization of lysozyme loaded niosomal formulations as a new controlled delivery system. Pharm Chem J. 2020; 53(10): 921-930.
  22. Damera DP, Nag A. Tuning the phase transition temperature of hybrid Span60-L64 thermoresponsive niosomes: Insights from fluorescence and Raman spectroscopy. J Mol Liq. 2021; 340(17): 117110.
  23. Jiao Y, Hannafon BN, Ding WQ. Disulfiram’s anticancer activity: evidence and mechanisms. Anticancer Agents Med Chem. 2016; 16(11): 1378-1384.
  24. Kelley KC, Grossman KF, Brittain-Blankenship M, Thorne KM, Akerley WL, Terrazas MC, et al. A phase 1 dose-escalation study of disulfiram and copper gluconate in patients with advanced solid tumors involving the liver using S-glutathionylation as a biomarker. BMC Cancer. 2021; 21(1): 510.
  25. Meraz-Torres F, Plöger S, Garbe C, Niessner H, Sinnberg T. Disulfiram as a therapeutic agent for metastatic malignant melanoma-old myth or new logos? Cancers (Basel). 2020; 12(12)3538.
  26. Jakola AS, Werlenius K, Mudaisi M, Hylin S, Kinhult S, Bartek J Jr, et al. Disulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT): Study protocol for a randomized controlled trial. F1000Res. 2018; 7: 1797.
  27. Paller CJ, Antonarakis ES. Management of biochemically recurrent prostate cancer after local therapy: evolving standards of care and new directions. Clin Adv Hematol Oncol. 2013; 11(1): 14-23.
  28. McMahon A, Chen W, Li F. Old wine in new bottles: advanced drug delivery systems for disulfiram-based cancer therapy. J Control Release. 2020; 319: 352-359.
  29. Patel J, Ketkar S, Patil S, Fearnley J, Mahadik KR, Paradkar AR. Potentiating antimicrobial efficacy of propolis through niosomalbased system for administration. Integr Med Res. 2015; 4(2): 94- 101.
  30. Huang X, Liao W, Zhang G, Kang S, Zhang CY. pH-sensitive micelles self-assembled from polymer brush (PAE-g-cholesterol)-b- PEG-b-(PAE-g-cholesterol) for anticancer drug delivery and controlled release. Int J Nanomedicine. 2017; 12: 2215-2226.
  31. Akbari V, Abedi D, Pardakhty A, Sadeghi-Aliabadi H. Release studies on ciprofloxacin loaded non-ionic surfactant vesicles. Avicenna J Med Biotechnol. 2015; 7(2): 69-75.
  32. Akbarzadeh I, Rezaei N, Bazzazan S, Mezajin MN, Mansouri A, Karbalaeiheidar H, et al. In silico and in vitro studies of GENT-EDTA encapsulated niosomes: A novel approach to enhance the antibacterial activity and biofilm inhibition in drug-resistant Klebsiella pneumoniae. Biomater Adv. 2023; 149: 213384.
Cell Journal (Yakhteh)
Volume 25, Issue 6
June 2023
Pages 407-417

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