Ukr.Biochem.J. 2026; Volume 98, Issue 2, Mar-Apr, pp. 85-95

Molecular evolution of biosynthesized selenium nanoparticles and their effect on oral squamous cell carcinoma

13.04.2026   Uncategorized

R. T. Al-Muswie1, M. N. Abdulsayed2, D. A. Alghezi3*,
B. A. Ghyadh4, A. J. Alfahdawi5

1Basic Science Department, College of Dentistry, University of Thi-Qar, Thi-Qar, Iraq;
2Otolaryngology-Head and Neck Department, College of Medicine,
University of Thi-Qar, Thi-Qar, Iraq;
3Microbiology Department, College of Medicine, University of Thi-Qar, Thi-Qar, Iraq;
4Biology Department, College of Science, University of Thi-Qar, Thi-Qar, Iraq;
5Department of Pathological Analysis, College of Applied Sciences,
University of Fallujah, Al-Anbar, Iraq;
*e-mail: Dhafer.a.f.alghezi@bath.edu

Received: 25 October 2025; Revised: 12 December 2025;
Accepted: 03 April 2026; Available on-line: April 2026

Cancer remains a predominant cause of mortality globally, and the suboptimal effectiveness of existing­ therapeutic modalities has catalyzed the exploration of novel treatment approaches. Nanomaterials, specifically selenium nanoparticles (SeNPs), have exhibited encouraging anticancer activity. This investigation aimed to evaluate the human oral squamous cell carcinoma (OSCC) cells viability and expression of prolifera­tion and apoptosis molecular markers under treatment with SeNPs. Selenium nanoparticles were synthesized with the use of Lactobacillus plantarum cultured in a medium containing selenium dioxide. The methods of energy-dispersive X-ray, scanning electron and atomic force microscopy were used to determine the SeNPs composition and three-dimensional images. MTT viability assay and qRT-PCR analysis of cyclin D1 and Bax gene expression were applied. OSCC cells were treated with SeNPs in a range of 25–200 µg/ml for 24 h. It was demonstrated that SeNPs induced a dose-dependent inhibition of cell viability with IC50 value of 97 μg/ml. At lower concentrations (25–50 µg/ml) SeNPs transiently suppressed Bax and elevated Cyclin D1 expression­, indicating the adaptive proliferative response. At higher concentrations (100–200 µg/ml), SeNPs induced apoptotic pathways and G1-phase cell cycle arrest, significantly upregulating Bax and downregulating­ Cyclin D1 expression. These findings underscore the Selenium nanoparticles potential as nanotherapeutic agents for OSCC treatment.

Keywords: , , ,

References:

  1. Tan Y, Wang Z, Xu M, Li B, Huang Z, Qin S, Nice EC, Tang J, Huang C. Oral squamous cell carcinomas: state of the field and emerging directions. Int J Oral Sci. 2023;15(1):44. PubMed, PubMedCentral, CrossRef
  2. Radhika T, Jeddy N, Nithya S, Muthumeenakshi RM. Salivary biomarkers in oral squamous cell carcinoma – An insight. J Oral Biol Craniofac Res. 2016;6(Suppl 1):S51-S54. PubMed, PubMedCentral, CrossRef
  3. Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med. 2001;345(26):1890-900. PubMed, CrossRef
  4. Khan S, Hossain MK. Classification and Properties of Nanoparticles. In: Nanoparticle-Based Polymer Composites. 2022. p. 15-54. CrossRef
  5. Varadavenkatesan T, Nagendran V, Vinayagam R, Goveas LC, Selvaraj R. Effective degradation of dyes using silver nanoparticles synthesized from Thunbergia grandiflora leaf extract. Bioresour Technol Rep. 2024;27:101914. CrossRef
  6. Ahmad Z, Shah SA, Khattak I, Ullah H, Khan AA, Shah RA, et al. Melia Azedarach impregnated Co and Ni zero-valent metal nanoparticles for organic pollutants degradation: validation of experiments through statistical analysis. J Mater Sci: Mater Electron. 2020;31:16938-16950. CrossRef
  7. Selvaraj R, Nagendran V, Varadavenkatesan T, Goveas LC, Vinayagam R. Stable silver nanoparticles synthesis using Tabebuia aurea leaf extract for efficient water treatment: A sustainable approach to environmental remediation. Chem Eng Res Des. 2024;208:456-463. CrossRef
  8. Rukhsar M, Ahmad Z, Rauf A, Zeb H, Ur-Rehman M, Hemeg HA. An Overview of Iron Oxide (Fe3O4) Nanoparticles: From Synthetic Strategies, Characterization to Antibacterial and Anticancer Applications. Crystals. 2022;12(12):1809. CrossRef
  9. Rauf A, Rashid U, Atta A, Khan I, Shah ZA, Mobeen B, Javed A, Alomar TS, Almasoud N, Naz S, Ahmad Z, Ribaudo G. Antiproliferative Activity of Lignans from Olea ferruginea: In Vitro Evidence Supported by Docking Studies. Front Biosci (Landmark Ed). 2023;28(9):216. PubMed, CrossRef
  10. Forootanfar H, Adeli-Sardou M, Nikkhoo M, Mehrabani M, Amir-Heidari B, Shahverdi AR, Shakibaie M. Antioxidant and cytotoxic effect of biologically synthesized selenium nanoparticles in comparison to selenium dioxide. J Trace Elem Med Biol. 2014;28(1):75-79. PubMed, CrossRef
  11. Skalickova S, Milosavljevic V, Cihalova K, Horky P, Richtera L, Adam V. Selenium nanoparticles as a nutritional supplement. Nutrition. 2017;33:83-90. PubMed, CrossRef
  12. Faghfuri E, Yazdi MH, Mahdavi M, Sepehrizadeh Z, Faramarzi MA, Mavandadnejad F, Shahverdi AR. Dose-response relationship study of selenium nanoparticles as an immunostimulatory agent in cancer-bearing mice. Arch Med Res. 2015;46(1):31-37. PubMed, CrossRef
  13. Yazdi MH, Mahdavi M, Varastehmoradi B, Faramarzi MA, Shahverdi AR. The immunostimulatory effect of biogenic selenium nanoparticles on the 4T1 breast cancer model: an in vivo study. Biol Trace Elem Res. 2012;149(1):22-28. PubMed, CrossRef
  14. Tugarova AV, Mamchenkova PV, Dyatlova YA, Kamnev AA. FTIR and Raman spectroscopic studies of selenium nanoparticles synthesised by the bacterium Azospirillum thiophilum. Spectrochim Acta A Mol Biomol Spectrosc. 2018;192:458-463. PubMed, CrossRef
  15. Winkler HC, Suter M, Naegeli H. Critical review of the safety assessment of nano-structured silica additives in food. J Nanobiotechnology. 2016;14(1):44. PubMed, PubMedCentral, CrossRef
  16. Liu S, Wei W, Wang J, Chen T. Theranostic applications of selenium nanomedicines against lung cancer. J Nanobiotechnology. 2023;21(1):96. PubMed, PubMedCentral, CrossRef
  17. Zhou Y, Xu M, Liu Y, Bai Y, Deng Y, Liu J, Chen L. Green synthesis of Se/Ru alloy nanoparticles using gallic acid and evaluation of theiranti-invasive effects in HeLa cells. Colloids Surf B Biointerfaces. 2016;144:118-124. PubMed, CrossRef
  18. Wang X, Sun K, Tan Y, Wu S, Zhang J. Efficacy and safety of selenium nanoparticles administered intraperitoneally for the prevention of growth of cancer cells in the peritoneal cavity. Free Radic Biol Med. 2014;72:1-10. PubMed, CrossRef
  19. Gao F, Yuan Q, Gao L, Cai P, Zhu H, Liu R, Wang Y, Wei Y, Huang G, Liang J, Gao X. Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles. Biomaterials. 2014;35(31):8854-8866. PubMed, CrossRef
  20. Zare H, Sanaei M, Yazdi MH, Shahverdi AR. Selenium Nanoparticle-Enriched Lactobacillus plantarum Causes More Anti-carcinogenic Effect on Human Colon Cancer Cells Compared to Non-enriched Ones. BioNanoScience. 2023;13:1110-1115. CrossRef
  21. Shakibaie M, Khorramizadeh MR, Faramarzi MA, Sabzevari O, Shahverdi AR. Biosynthesis and recovery of selenium nanoparticles and the effects on matrix metalloproteinase-2 expression. Biotechnol Appl Biochem. 2010;56(1):7-15. PubMed, CrossRef
  22. Shield KD, Ferlay J, Jemal A, Sankaranarayanan R, Chaturvedi AK, Bray F, Soerjomataram I. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin. 2017;67(1):51-64. PubMed, CrossRef
  23. Speight PM. Update on oral epithelial dysplasia and progression to cancer. Head Neck Pathol. 2007;1(1):61-66. PubMed, PubMedCentral, CrossRef
  24. Jayaraj G, Ramani P, Sherlin HJ, Premkumar P, Anuja N. Inter-observer agreement in grading oral epithelial dysplasia – A systematic review. J Oral Maxillofac Surg Med Pathol. 2015;27(1):112-116. CrossRef
  25. Astekar M, Metgud R, Sharma A, Soni A. Hidden keys in stroma: Unlocking the tumor progression. Oral Maxillofac Pathol. 2013;17(1):82-88. PubMed, PubMedCentral, CrossRef
  26. Alghezi DA, Aljawher R, Al-Musawi S. Increased CD73 expression is associated with poorly differentiated Gleason score and tumor size in prostate cancer. J Adv Biotechnol Exp Ther. 2023;6(1):161-171. CrossRef
  27. Sonkusre P, Cameotra SS. Biogenic selenium nanoparticles induce ROS-mediated necroptosis in PC-3 cancer cells through TNF activation. J Nanobiotechnology. 2017;15(1):43. PubMed, PubMedCentral, CrossRef
  28. Xia Y, You P, Xu F, Liu J, Xing F. Novel Functionalized Selenium Nanoparticles for Enhanced Anti-Hepatocarcinoma Activity In vitro. Nanoscale Res Lett. 2015;10(1):1051. PubMed, PubMedCentral, CrossRef
  29. Patrón-Romero L, Luque-Morales PA, Loera-Castañeda V, Lares-Asseff I, Leal-Ávila MÁ, Alvelais-Palacios JA, Plasencia-López I, Almanza-Reyes H. Mitochondrial Dysfunction Induced by Zinc Oxide Nanoparticles. Crystals. 2022;12(8):1089. CrossRef
  30. Wang J, Liu N, Su Q, Lv Y, Yang C, Zhan H. Green Synthesis of Gold Nanoparticles and Study of Their Inhibitory Effect on Bulk Cancer Cells and Cancer Stem Cells in Breast Carcinoma. Nanomaterials (Basel). 2022;12(19):3324. PubMed, PubMedCentral, CrossRef
  31. Zeng D, Zhao J, Luk KH, Cheung ST, Wong KH, Chen T. Potentiation of in Vivo Anticancer Efficacy of Selenium Nanoparticles by Mushroom Polysaccharides Surface Decoration. J Agric Food Chem. 2019;67(10):2865-2876. PubMed, CrossRef
  32. Liao G, Tang J, Wang D, Zuo H, Zhang Q, Liu Y, Xion H. Selenium nanoparticles (SeNPs) have potent antitumor activity against prostate cancer cells through the upregulation of miR-16. World J Surg Oncol. 2020;18(1):81. PubMed, PubMedCentral, CrossRef
  33. Varlamova EG. Molecular Mechanisms of the Therapeutic Effect of Selenium Nanoparticles in Hepatocellular Carcinoma. Cells. 2024;13(13):1102.PubMed, PubMedCentral, CrossRef
  34. Tian J, Wei X, Zhang W, Xu A. Effects of Selenium Nanoparticles Combined With Radiotherapy on Lung Cancer Cells. Front Bioeng Biotechnol. 2020;8:598997. PubMed, PubMedCentral, CrossRef
  35. Tang G, Zhen Y, Xie W, Wang Y, Chen F, Qin C,Yang H, Du Z, Shen Z, Zhang B, Wu Z, Tian D, Hu H. Preoperative hemoglobin-platelet ratio can significantly predict progression and mortality outcomes in patients with T1G3 bladder cancer undergoing transurethral resection of bladder tumor. Oncotarget. 2018;9(26):18627-18636. PubMed, PubMedCentral, CrossRef
  36. Nori-Garavand R, Hormozi M, Narimani L, Beigi Boroujeni N, Rajabzadeh A, Zarei L, Beigi Boroujeni M, Beigi Boroujeni M. Effect of Selenium on Expression of Apoptosis-Related Genes in Cryomedia of Mice Ovary after Vitrification. Biomed Res Int. 2020;2020:5389731. PubMed, PubMedCentral, CrossRef
  37. Alkhudhayri AA, Wahab R, Siddiqui MA, Ahmad J. Selenium Nanoparticles Induce Cytotoxicity and Apoptosis in Human Breast Cancer (MCF-7) and Liver (HepG2) Cell Lines. Nanosci Nanotechnol Lett. 2020;12:324-330. CrossRef
  38. Assoian RK, Klein EA. Growth control by intracellular tension and extracellular stiffness. Trends Cell Biol. 2008;18(7):347-352. PubMed, PubMedCentral, CrossRef
  39. Donnellan R, Chetty R. Cyclin D1 and human neoplasia. Mol Pathol. 1998;51(1):1-7. PubMed, PubMedCentral, CrossRef
  40. Alao JP. The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Mol Cancer. 2007;6:24. PubMed, PubMedCentral, CrossRef
  41. Wadhwani SA, Shedbalkar UU, Singh R, Chopade BA. Biogenic selenium nanoparticles: current status and future prospects. Appl Microbiol Biotechnol. 2016;100(6):2555-2566. PubMed, CrossRef
  42. Hosnedlova B, Kepinska M, Skalickova S, Fernandez C, Ruttkay-Nedecky B, Peng Q, Baron M, Melcova M, Opatrilova R, Zidkova J, Bjørklund G, Sochor J, Kizek R. Nano-selenium and its nanomedicine applications: a critical review. Int J Nanomedicine. 2018;13:2107-2128. PubMed, PubMedCentral, CrossRef
  43. Huang G, Liu Z, He L, Luk KH, Cheung ST, Wong KH, Chen T. Autophagy is an important action mode for functionalized selenium nanoparticles to exhibit anti-colorectal cancer activity. Biomater Sci. 2018;6(9):2508-2517. PubMed, CrossRef
  44. Vekariya KK, Kaur J, Tikoo K. ERα signaling imparts chemotherapeutic selectivity to selenium nanoparticles in breast cancer. Nanomedicine. 2012;8(7):1125-1132. PubMed, CrossRef
  45. Al-Muswie RT, Enayah SH, Ghaleb RA. Synergistic effects of Cassia fistula extract combination with cisplatin on the regulation of microRNA-145 and gene expression in colon cancer cell line SW480. Med J Babylon. 2023;20(4):670-680. CrossRef
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