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Synthesis of Gingerol-loaded Uio-66 nanoparticles and its anti-cancer effect against gastric cancer cell line (AGS)

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Abstract

Background

Gastric cancer is the world’s fifth most prevalent cancer and its treatments are associated with issues. In this investigation, a UIO-66 nanoparticle was loaded with Gingerol (UIO-66-Gin) as a great drug carrier vehicle for chemotherapy of the AGS cancer cell lines.

Methods and Results

UIO-66-Gin characterization was performed using SEM, DLS and FTIR tests. The release profile of Gin from UIO-66 was also assessed. The cytotoxicity of UIO-66-Gin against AGS cells was assessed using MTT assay. Caspase3, Caspase9, Bax, and Bcl2 genes expression was evaluated via Real-time PCR and apoptosis rate was performed using flow-cytometry assay. Size analysis indicated the spherical shape of nano-formulation with the mean size of 174.3 nm. Release analysis indicated that there was a 50% Gin release from the nanocarrier was reported in roughly 21 h, which revealed the regulated release of bioactive compound from the UIO-66 formulation in PBS medium. After 48 and 72 h, various concentration of both the Gin and UIO-66-Gin started to induce cytotoxicity in cancerous cells. However, the induction of cytotoxicity was higher in cells treated with UIO-66-Gin. UIO-66-Gin could induce the expression of pro-apoptotic (Bax, Caspase3, and Caspase9) genes and down-regulate the expression of Bcl2 as anti-apoptotic gene rather than other formulation. Flowcytometry results indicated that the elevation of apoptotic rate in cells treated with UIO-66-Gin was significantly higher than Gin treated cells.

Conclusions

Our investigation revealed the potent anticancer effect and apoptotic induction ability of UIO-66-Gin against cancerous cells through altering the expression of genes involved in apoptosis.

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Abbreviations

Bax :

Bcl2 Associated X

Bcl2 :

B-cell lymphoma 2

AKT :

serine/threonine-specific protein kinase

DLS:

Dynamic Light Scattering

SEM:

Scanning Electron Microscope

FTIR:

Fourier transform infrared

FITC:

Fluorescein isothiocyanate

PS:

phytosiderophores

ZIF-8:

Zeolitic imidazolate framework-8

UIO-66:

Zirconium 1,4-dicarboxybenzene MOF

References

  1. Hamashima C (2020) The burden of gastric cancer. Annals of translational medicine 8

  2. Tan MC, Graham DY (2019) Gastric cancer risk stratification and surveillance after Helicobacter pylori eradication: 2020. Gastrointest Endosc 90:457–460

    Article  PubMed  PubMed Central  Google Scholar 

  3. Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R (2020) Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci 21:4012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yang L, Ying X, Liu S et al (2020) Gastric cancer: Epidemiology, risk factors and prevention strategies. Chin J Cancer Res 32:695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mashhadi NS, Ghiasvand R, Askari G, Hariri M, Darvishi L, Mofid MR (2013) Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence. Int J Prev Med 4:S36

    PubMed  PubMed Central  Google Scholar 

  6. Wang X, Shen Y, Thakur K et al (2020) Antibacterial activity and mechanism of ginger essential oil against Escherichia coli and Staphylococcus aureus. Molecules 25:3955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Osaro-Matthew R, Ire F, Frank-Peterside N (2020) Screening of actinomycetes from turmeric (Curcuma longa L.) and ginger (Zingiber officinale) rhizosphere for antifungal activity. J Adv Microbiol 20:18–28

    Article  Google Scholar 

  8. Ahmed SHH, Gonda T, Hunyadi A (2021) Medicinal chemistry inspired by ginger: exploring the chemical space around 6-gingerol. RSC Adv 11:26687–26699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Xu S, Zhang H, Liu T et al (2020) 6-Gingerol induces cell-cycle G1-phase arrest through AKT–GSK 3β–cyclin D1 pathway in renal-cell carcinoma. Cancer Chemother Pharmacol 85:379–390

    Article  CAS  PubMed  Google Scholar 

  10. Chatupheeraphat C, Nantasenamat C, Deesrisak K, Roytrakul S, Anurathapan U, Tanyong D (2020) Bioinformatics and experimental studies of anti-leukemic activity from 6-gingerol demonstrate its role in p53 mediated apoptosis pathway. EXCLI J 19:582

    PubMed  PubMed Central  Google Scholar 

  11. Karatay KB, Kılçar AY, Derviş E, Müftüler FZB (2020) Radioiodinated ginger compounds (6-gingerol and 6-shogaol) and incorporation assays on breast cancer cells. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 20:1129–1139

  12. Manatunga DC, de Silva RM, de Silva K, Wijeratne DT, Malavige GN, Williams G (2018) Fabrication of 6-gingerol, doxorubicin and alginate hydroxyapatite into a bio-compatible formulation: enhanced anti-proliferative effect on breast and liver cancer cells. Chem Cent J 12:1–13

    Article  Google Scholar 

  13. Cao J, Li X, Tian H (2020) Metal-organic framework (MOF)-based drug delivery. Curr Med Chem 27:5949–5969

    Article  CAS  PubMed  Google Scholar 

  14. Ge X, Wong R, Anisa A, Ma S (2021) Recent development of metal-organic framework nanocomposites for biomedical applications.Biomaterials,121322

  15. Hoop M, Walde CF, Riccò R et al (2018) Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications. Appl Mater Today 11:13–21

    Article  Google Scholar 

  16. Celeste A, Paolone A, Itié J-P et al (2020) Mesoporous metal–organic framework MIL-101 at high pressure. J Am Chem Soc 142:15012–15019

    Article  CAS  PubMed  Google Scholar 

  17. Liu X (2020) Metal-organic framework UiO-66 membranes. Front Chem Sci Eng 14:216–232

    Article  CAS  Google Scholar 

  18. Pirzadeh K, Esfandiari K, Ghoreyshi AA, Rahimnejad M (2020) CO2 and N2 adsorption and separation using aminated UiO-66 and Cu3 (BTC) 2: A comparative study. Korean J Chem Eng 37:513–524

    Article  CAS  Google Scholar 

  19. Chowdhuri AR, Laha D, Chandra S, Karmakar P, Sahu SK (2017) Synthesis of multifunctional upconversion NMOFs for targeted antitumor drug delivery and imaging in triple negative breast cancer cells. Chem Eng J 319:200–211

    Article  CAS  Google Scholar 

  20. Rakhshani N, Hassanzadeh Nemati N, Ramezani Saadat Abadi A, Sadrnezhaad S (2021) Fabrication and evaluation of controlled release of Doxorubicin loaded UiO-66-NH2 metal organic frameworks.International Journal of Engineering34

  21. Tulig K, Walton KS (2014) An alternative UiO-66 synthesis for HCl-sensitive nanoparticle encapsulation. RSC Adv 4:51080–51083

    Article  CAS  Google Scholar 

  22. Akbarzadeh I, Shayan M, Bourbour M et al (2021) Preparation, optimization and in-vitro evaluation of curcumin-loaded niosome@ calcium alginate nanocarrier as a new approach for breast cancer treatment. Biology 10:173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dabbagh Moghaddam F, Akbarzadeh I, Marzbankia E et al (2021) Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect. Cancer Nanotechnol 12:1–35

    Article  Google Scholar 

  24. Nafees S, Zafaryab M, Mehdi SH, Zia B, Rizvi MA, Khan MA (2021) Anti-cancer effect of gingerol in cancer prevention and treatment. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 21:428–432

  25. Furlan V, Bren U (2020) Protective effects of [6]-gingerol against chemical carcinogens: mechanistic insights. Int J Mol Sci 21:695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Suresh K, Matzger AJ (2019) Enhanced drug delivery by dissolution of amorphous drug encapsulated in a water unstable metal–organic framework (MOF). Angew Chem Int Ed 58:16790–16794

    Article  CAS  Google Scholar 

  27. Nasrabadi M, Ghasemzadeh MA, Monfared MRZ (2019) The preparation and characterization of UiO-66 metal–organic frameworks for the delivery of the drug ciprofloxacin and an evaluation of their antibacterial activities. New J Chem 43:16033–16040

    Article  CAS  Google Scholar 

  28. Markopoulou P, Panagiotou N, Li A et al (2020) Identifying differing intracellular cargo release mechanisms by monitoring in vitro drug delivery from MOFs in real time. Cell Rep Phys Sci 1:100254

    Article  PubMed  PubMed Central  Google Scholar 

  29. McIlwain DR, Berger T, Mak TW (2013) Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 5:a008656

    Article  PubMed  PubMed Central  Google Scholar 

  30. Campbell KJ, Tait SW (2018) Targeting BCL-2 regulated apoptosis in cancer. Open biology 8:180002

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sp N, Kang DY, Lee J-M, Bae SW, Jang K-J (2021) Potential antitumor effects of 6-gingerol in p53-dependent mitochondrial apoptosis and inhibition of tumor sphere formation in breast cancer cells. Int J Mol Sci 22:4660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Martin ACB, Fuzer AM, Becceneri AB et al (2017) [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo. Oncotarget 8:72260

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhang L, Lei J, Ma F, Ling P, Liu J, Ju H (2015) A porphyrin photosensitized metal–organic framework for cancer cell apoptosis and caspase responsive theranostics. Chem Commun 51:10831–10834

    Article  CAS  Google Scholar 

  34. Mohammed MS (2021) The Molecular Activity of Gingerol on Inhibits Proliferation of Breast Cancer Cell Line (MCF7) Through Caspase Activity. Annals of the Romanian Society for Cell Biology, pp 11095–11103

  35. Justus CR, Dong L, Yang LV (2013) Acidic tumor microenvironment and pH-sensing G protein-coupled receptors. Front Physiol 4:354

    Article  PubMed  PubMed Central  Google Scholar 

  36. Li L, Ji Y, Ma Y-X, Gao L-Q, Zhou H-G, Wu M-H (2019) 6-Gingerol inhibits proliferation in gastric cancer via the STAT3 pathway in vitro. Cellular and Molecular Biology. France) 65:109–113(Noisy-le-Grand

    Google Scholar 

  37. Hu SM, Yao XH, Hao YH, Pan AH, Zhou XW (2020) 8–Gingerol regulates colorectal cancer cell proliferation and migration through the EGFR/STAT/ERK pathway. Int J Oncol 56:390–397

    CAS  PubMed  Google Scholar 

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Biology, Tehran North Branch, Islamic Azad University, 16511-53311, Tehran, Iran

    Irana Kazazi & Fatemeh Ashrafi

  2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Maryam Malekloo

Authors
  1. Irana Kazazi
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  2. Fatemeh Ashrafi
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  3. Maryam Malekloo
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Irana Kazazi, Fatemeh Ashrafi and Maryam Malekloo. The first draft of the manuscript was written by Irana Kazazi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Fatemeh Ashrafi.

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Kazazi, I., Ashrafi, F. & Malekloo, M. Synthesis of Gingerol-loaded Uio-66 nanoparticles and its anti-cancer effect against gastric cancer cell line (AGS). Mol Biol Rep 50, 3503–3513 (2023). https://doi.org/10.1007/s11033-022-07667-9

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