Skip to main content

Advertisement

Log in

Herniarin-loaded solid lipid nanoparticles: promising molecular mechanism and therapeutic potential against pancreatic cancer line

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

The notion of cancer therapy is intrinsically subjected to multiple challenges due to the drug resistance and drug toxicity for normal tissues. Herniarin (7-methoxycoumarin) belongs to the naturally occurring aromatic phytochemicals and coumarins. Considering the boosting effect of nanocarriers in drug delivery, we investigated the proapoptotic, anti-metastatic properties, and molecular mechanism of herniarin-loaded solid lipid nanoparticles on human gastric adenocarcinoma (AGS), human colon adenocarcinoma (HT-29), human pancreatic carcinoma (Panc-1), and normal human skin fibroblast (HFF) cell lines.

Methods and results

The cytotoxicity of synthesized nanoparticle have been tested using MTT assay. The obtained results manifested that concentration of herniarin that exerts 50% cell growth inhibition (IC50) against HT-29, AGS, and Panc-1 was calculated 138.34, 123.46, and 83.744 µL, respectively. Given that nanoparticles showed lowest IC50 values on Panc-1 cell line, these cells were selected for further analysis. The apoptosis induction and cell cycle arrest were examined performing real-time PCR, flow cytometry, and DAPI/acridine orange-propidium iodide staining. The expression of apoptosis-related genes, including BCL-2, was decreased, while the expression of CASP9, CASP8, and CASP3 was increased in response to the treatment. Moreover, the expression of metastasis-related gene (MMP2) was significantly suppressed under Her-SLN-NPs treatment. According to the flow cytometry findings, we observed no cell cycle arrest at any stage.

Conclusion

Our funding manifested herniarin encapsulated solid lipid nanoparticles has potent therapeutic target against Panc-1 cell line.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Al-Ishaq RK, Overy AJ, Büsselberg DJB (2020) Phytochemicals and gastrointestinal cancer: cellular mechanisms and effects to change cancer progression. Biomolecules 10(1):105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Carneiro A et al (2022) Discriminating epithelial to mesenchymal transition phenotypes in circulating tumor cells isolated from advanced gastrointestinal cancer patients. Cells 11(3):376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Banikazemi Z et al (2021) Coumarins and gastrointestinal cancer: a new therapeutic option? Front Oncol 11:4107

    Article  Google Scholar 

  4. Küpeli Akkol E et al (2020) Coumarins and coumarin-related compounds in pharmacotherapy of cancer. Cancers 12(7):1959

    Article  PubMed  PubMed Central  Google Scholar 

  5. Banikazemi Z et al (2021) Coumarins and gastrointestinal cancer: a new therapeutic option? Front Oncol 11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Singh D, Rahman M (2020) Umbelliferone loaded nanocarriers for healthcare applications. Curr Biochem Eng 6(1):25–33

    Article  CAS  Google Scholar 

  7. Salehcheh M et al (2022) The protective effect of herniarin on genotoxicity and apoptosis induced by cisplatin bone marrow cells of rats. Drug Chem Toxicol 45(4):1470–1475

    Article  CAS  PubMed  Google Scholar 

  8. Haneef J, Ali S, Chadha RJAP (2021) Emerging multi-drug eutectics: opportunities and challenges. AAPS Pharm Sci Tech 22:1–17

    Article  Google Scholar 

  9. Saka R, Chella N (2021) Nanotechnology delivery of natural therapeutic substances: a review. Environ Chem Lett 19:1097–1106

    Article  CAS  Google Scholar 

  10. Ghasemiyeh P, Mohammadi-Samani S (2018) Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci 13(4):288

    Article  PubMed  PubMed Central  Google Scholar 

  11. Shirodkar RK et al (2019) Solid lipid nanoparticles and nanostructured lipid carriers: emerging lipid based drug delivery systems. Pharm Chem J 53(5):440–453

    Article  CAS  Google Scholar 

  12. Bose P, Pattanayak SP, Priyam A (2020) Herniarin, a natural coumarin loaded novel targeted plasmonic silver nanoparticles for light activated chemo-photothermal therapy in preclinical model of breast cancer. Pharmacogn Mag 16(5):474

    Article  Google Scholar 

  13. Vijayalakshmi A, Sindhu G (2017) Umbelliferone arrest cell cycle at G0/G1 phase and induces apoptosis in human oral carcinoma (KB) cells possibly via oxidative DNA damage. Biomed Pharmacother 92:661–671

    Article  CAS  PubMed  Google Scholar 

  14. Liang Y et al (2018) CD36 plays a critical role in proliferation, migration and tamoxifen-inhibited growth of ER-positive breast cancer cells. Oncogenesis 7(12):1–14

    Article  Google Scholar 

  15. Cheng K-C et al (2007) Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction. BMC genomics 8(1):1–17

    Article  Google Scholar 

  16. Wagner MS et al (2018) Revitalizing the AZT through of the selenium: an approach in human triple negative breast cancer cell line. Front Oncol 8:525

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rahmani F, Karimi E, Oskoueian E (2020) synthesis and characterisation of chitosan-encapsulated genistein: its anti-proliferative and anti-angiogenic activities. J microencapsul 37(4):305–313

    Article  CAS  PubMed  Google Scholar 

  18. Sun Y-p et al (2014) Synovium fragment-derived cells exhibit characteristics similar to those of dissociated multipotent cells synovial fluid of the temporomandibular joint. Plos One 9(7):e101896

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gong W-Y et al (2014) Flavonoid components in Scutellaria baicalensis inhibit nicotine-induced proliferation, metastasis and lung cancer-associated inflammation in vitro. Inter J oncol 44(5):1561–1570

    Article  CAS  Google Scholar 

  20. Peng F et al (2022) Regulated cell death (RCD) in cancer: key pathways and targeted therapies. Signal Transduct Target Ther 7(1):1–66

    Google Scholar 

  21. Pistritto G et al (2016) Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging 8(4):603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Winer A, Adams S, Mignatti PJMct (2018) Matrix metalloproteinase inhibitors in cancer therapy: turning past failures into future successes matrix metalloproteinase inhibitors in cancer therapy. Mol Cancer Ther 17(6):1147–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang S et al (2019) Matrix metalloproteinase expressions play important role in prediction of ovarian cancer outcome. Sci Rep 9(1):11677

    Article  PubMed  PubMed Central  Google Scholar 

  24. Honary S, Zahir F (2013) Effect of zeta potential on the properties of nano-drug delivery systems-a review (part 2). Trop J Pharm Res 12(2):265–273

    Google Scholar 

  25. Honary S, Zahir F (2013) Effect of zeta potential on the properties of nano-drug delivery systems-a review (part 1). Trop J Pharm Res 12(2):255–264

    Google Scholar 

  26. Li S-D, Huang L (2008) Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm 5(4):496–504

    Article  CAS  PubMed  Google Scholar 

  27. Tabatabaeain SF, Karimi E, Hashemi M (2022) Satureja khuzistanica essential oil-loaded solid lipid nanoparticles modified with chitosan-folate: evaluation of encapsulation efficiency, cytotoxic and pro-apoptotic properties. Front Chem 10:904973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Thakkar A et al (2015) Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. Int J Oncol 46(4):1827–1834

    Article  CAS  PubMed  Google Scholar 

  29. Mousavi SH et al (2015) Comparative analysis of the cytotoxic effect of 7-prenyloxycoumarin compounds and herniarin on MCF-7 cell line. Avicenna J Phytomed 5(6):520

    CAS  PubMed  PubMed Central  Google Scholar 

  30. KIEŁBUS M et al (2013) 7-substituted coumarins inhibit proliferation and migration of laryngeal cancer cells in vitro. Anticancer Res 33(10):4347–4356

    PubMed  Google Scholar 

  31. Haghighitalab A et al (2014) Enhancement of cisplatin cytotoxicity in combination with herniarin in vitro. Drug Chem Toxicol 37(2):156–162

    Article  CAS  PubMed  Google Scholar 

  32. Kong D, Zhang Z (2019) PI3K/AKT inhibitors as sensitizing agents for cancer chemotherapy. Protein kinase inhibitors as sensitizing agents for chemotherapy. Elsevier, Amsterdam, pp 187–205

    Book  Google Scholar 

  33. Prabhu L et al (2014) Critical role of NF-κB in pancreatic cancer. Oncotarget 5(22):10969

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhang Y et al (2020) MicroRNA–23b–3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF–κB signaling pathways. Oncol Lett 20(5):1–1

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Islamic Azad University of Mashhad for the laboratory facilities.

Funding

The authors have not disclosed any funding.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Ehsan Karimi or Shirin Farivar.

Ethics declarations

Competing interest

The authors have not disclosed any competing interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Not applicable.

Research involving human participants and/or animals

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Delkhah, A., Karimi, E. & Farivar, S. Herniarin-loaded solid lipid nanoparticles: promising molecular mechanism and therapeutic potential against pancreatic cancer line. Mol Biol Rep 50, 6469–6479 (2023). https://doi.org/10.1007/s11033-023-08560-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-023-08560-9

Keywords

Navigation