Display options
Share it on

Asian Pac J Cancer Prev. 2021 Aug 01;22(8):2587-2596. doi: 10.31557/APJCP.2021.22.8.2587.

Anticancer Potential of Silibinin Loaded Polymeric Nanoparticles against Breast Cancer Cells: Insight into the Apoptotic Genes Targets.

Asian Pacific journal of cancer prevention : APJCP

Ali Pourgholi, Mehdi Dadashpour, Akram Mousapour, Akram Firouzi Amandi, Nosratollah Zarghami

Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, TR North Cyprus, Turkey.
  2. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
  3. Department of Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
  4. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
  5. Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz, Iran.
  6. Department of medicine, Faculty of medicine, Istanbul Aydin University, Istanbul, Turkey.
  7. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

PMID: 34452574 PMCID: PMC8629447 DOI: 10.31557/APJCP.2021.22.8.2587

Abstract

Silibinin (SIL) is a natural polyphenolic flavonoid with multiple biological and anti-cancer features. However, the complex hydrophobic nature and inadequate bioavailability of SIL hinder its efficiency at tumor sites. Investigating the possibility of an extensive strategy for better treatment of breast cancer, we carried out a comparative exploration of the inhibitory effect of SIL and SIL loaded PLGA-PEG nanoparticle (SIL-NPs) on the expression of the proapoptotic target genes, which is considered as an influential molecular target for treatment of breast cancer. The main diameter of SIL-NPs was 220 ± 6.37 and 150 ± 23.14 nm via DLS and FE-SEM respectively. Furthermore, the zeta potential of PLGA-PEG and SIL-NPs was -5.48±0.13 and -6.8±0.26 mV respectively. SIL encapsulation efficiency and drug release were determined by about 82.32 % by analyzing the calibration curve of SIL absorbance at 570 nm. Cytotoxicity of SIL and SIL-NPs was conducted by MTT assay after 24, 48, and 72 h of exposure times, and the gene expression levels of apoptotic genes, p53 and hTERT was measured by real-time PCR. Evaluation of drug toxicity revealed that SIL-NPs represents higher cytotoxic effects than pure SIL in a time and dose-dependent manner. Moreover, the results demonstrated that SIL-NPs could induce apoptosis in breast cancer cells by upregulation of caspase-3, caspase-7, p53 and Bax, along with Bcl-2, hTERT, survivin and Cyclin D1 down regulation. Our results indicated that PLGA-PEG can be used as stable carriers in nano-dimensions and SIL-NPs can be considered as a promising pharmacological agent for cancer therapy.
.

Keywords: Apoptosis; PLGA-PEG; Polymeric nanoparticles; breast cancer; silibinin

References

  1. NPJ Breast Cancer. 2020 Feb 5;6:5 - PubMed
  2. Drug Res (Stuttg). 2017 Sep;67(9):509-514 - PubMed
  3. Phytother Res. 2017 Nov;31(11):1651-1668 - PubMed
  4. J Biomed Res. 2016 Nov;30(6):452-465 - PubMed
  5. Environ Mol Mutagen. 2020 Apr;61(4):445-455 - PubMed
  6. Drug Res (Stuttg). 2018 Dec;68(12):710-716 - PubMed
  7. Pathol Res Pract. 2021 Jul;223:153452 - PubMed
  8. Arch Med Res. 2018 May;49(4):226-234 - PubMed
  9. Cancer Cell Int. 2014 Dec 23;14:66 - PubMed
  10. Anticancer Drugs. 2015 Jun;26(5):487-97 - PubMed
  11. Sci Rep. 2019 Feb 4;9(1):1306 - PubMed
  12. Asian Pac J Cancer Prev. ;18(5):1283-1287 - PubMed
  13. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):737-746 - PubMed
  14. Lancet. 2019 Sep 28;394(10204):1159-1168 - PubMed
  15. Adv Enzyme Regul. 2010;50(1):375-99 - PubMed
  16. Mater Sci Eng C Mater Biol Appl. 2020 Nov;116:111225 - PubMed
  17. Int J Mol Sci. 2019 May 03;20(9): - PubMed
  18. J BUON. 2016 Jul-Aug;21(4):917-924 - PubMed
  19. Artif Cells Nanomed Biotechnol. 2018 Aug;46(5):917-925 - PubMed
  20. Nutr Cancer. 2017 Nov-Dec;69(8):1290-1299 - PubMed
  21. Mol Cell Biochem. 2020 Jan;463(1-2):189-201 - PubMed
  22. Acta Pharmacol Sin. 2017 Feb;38(2):277-289 - PubMed
  23. Artif Cells Nanomed Biotechnol. 2017 Dec;45(8):1649-1656 - PubMed
  24. Nutr Cancer. 2019;71(7):1201-1213 - PubMed
  25. Biomed Pharmacother. 2019 Aug;116:109004 - PubMed
  26. Sci Transl Med. 2012 Jun 13;4(138):138ra79 - PubMed
  27. Iran J Pharm Res. 2016 Summer;15(3):421-433 - PubMed
  28. Mater Sci Eng C Mater Biol Appl. 2019 Nov;104:110007 - PubMed
  29. Phytomedicine. 2020 Nov;78:153309 - PubMed
  30. J Control Release. 2021 Feb 10;330:1046-1070 - PubMed
  31. Asian Pac J Cancer Prev. 2018 Apr 25;19(4):977-982 - PubMed
  32. Biomed Pharmacother. 2018 Sep;105:1026-1032 - PubMed
  33. J Mater Sci Mater Med. 2007 Oct;18(10):2067-73 - PubMed
  34. Am J Transl Res. 2019 Mar 15;11(3):1748-1759 - PubMed
  35. Mater Sci Eng C Mater Biol Appl. 2014 Aug 1;41:274-82 - PubMed
  36. Pathol Res Pract. 2020 Nov;216(11):153220 - PubMed
  37. J Cell Physiol. 2019 Dec;234(12):22285-22298 - PubMed
  38. Breast Cancer Res Treat. 2018 Nov;172(2):505 - PubMed
  39. Mol Med Rep. 2018 Aug;18(2):1835-1841 - PubMed
  40. J Cancer Res Ther. 2021 Apr-Jun;17(2):348-352 - PubMed

Publication Types