Crocin Inhibit the Metastasis of MDA-MB-231 Cell Line by Suppressing Epithelial to Mesenchymal Transition Through WNT/β-catenin Signalling Pathway

Overview

Journal Ann Med Surg (Lond)

Publisher Wolters Kluwer

Specialty Medical Education

Date 2024 Mar 11

PMID 38463069

Authors

Vajihe Ghorbanzadeh

Karwan Anwar Hassan Aljaf

Hunar Mustafa Wasman

Hassan Dariushnejad

Affiliations

Soon will be listed here.

Abstract

Background: Triple-negative breast cancer has the poorest prognosis and survival rates compared to other breast cancer subtypes due to its invasive behaviours. This type of cancer does not respond to biological therapies and exhibits resistance to available treatment options. Therefore, it is imperative to discover new therapeutics to address this challenge.

Methods: In this study, a TNBC cell line was utilized to investigate the anti-metastatic effect of crocin on the Wnt/β-catenin pathway. Cell proliferation was assessed using the MTT assay, and the effects of crocin on migration were monitored through transwell and wound healing experiments. The expression of specific epithelial-mesenchymal transition marker genes was evaluated using real-time polymerase chain reaction, and β-catenin expression was also examined through real-time polymerase chain reaction.

Results: The findings revealed that crocin significantly inhibits cell proliferation and migration of tumour cells in a dose-dependent manner. Moreover, crocin decreased the expression of Vimentin, Snail, Zeb-1, and β-catenin. Additionally, crocin increased the expression of E-cadherin in the MDA-MB-231 cell line.

Conclusions: The results demonstrated an association between crocin and the Wnt/β-catenin signalling pathway. In conclusion, this study establishes that crocin holds promise as a potential therapeutic option for triple-negative breast cancer.

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References

Obidiro O, Battogtokh G, Akala E . Triple Negative Breast Cancer Treatment Options and Limitations: Future Outlook. Pharmaceutics. 2023; 15(7). PMC: 10384267. DOI: 10.3390/pharmaceutics15071796. View

Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z, Falanga V . Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay. J Invest Dermatol. 2017; 137(2):e11-e16. DOI: 10.1016/j.jid.2016.11.020. View

Bakshi H, Quinn G, Nasef M, Mishra V, Aljabali A, El-Tanani M . Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways. Cells. 2022; 11(9). PMC: 9104358. DOI: 10.3390/cells11091502. View

Wang C, Chen Z, Zhou Y, Huang W, Zhu H, Mao F . T1a triple negative breast cancer has the worst prognosis among all the small tumor (<1 cm) of TNBC and HER2-rich subtypes. Gland Surg. 2021; 10(3):943-952. PMC: 8033067. DOI: 10.21037/gs-20-762. View

Veisi A, Akbari G, Mard S, Badfar G, Zarezade V, Mirshekar M . Role of crocin in several cancer cell lines: An updated review. Iran J Basic Med Sci. 2020; 23(1):3-12. PMC: 7206843. DOI: 10.22038/IJBMS.2019.37821.8995. View

Lashgarian H, Adamii V, Ghorbanzadeh V, Chodari L, Kamali F, Akbari S . Silibinin Inhibit Cell Migration through Downregulation of RAC1 Gene Expression in Highly Metastatic Breast Cancer Cell Line. Drug Res (Stuttg). 2020; 70(10):478-483. DOI: 10.1055/a-1223-1734. View

Sferrazza G, Corti M, Brusotti G, Pierimarchi P, Temporini C, Serafino A . Nature-derived compounds modulating Wnt/ -catenin pathway: a preventive and therapeutic opportunity in neoplastic diseases. Acta Pharm Sin B. 2020; 10(10):1814-1834. PMC: 7606110. DOI: 10.1016/j.apsb.2019.12.019. View

Amerizadeh F, Rezaei N, Rahmani F, Hassanian S, Moradi-Marjaneh R, Fiuji H . Crocin synergistically enhances the antiproliferative activity of 5-flurouracil through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer. J Cell Biochem. 2018; 119(12):10250-10261. DOI: 10.1002/jcb.27367. View

Ke D, El-Sahli S, Wang L . The Potential of Natural Products in the Treatment of Triple-negative Breast Cancer. Curr Cancer Drug Targets. 2021; 22(5):388-403. DOI: 10.2174/1568009622666211231140623. View

10.

Lyamina S, Baranovskii D, Kozhevnikova E, Ivanova T, Kalish S, Sadekov T . Mesenchymal Stromal Cells as a Driver of Inflammaging. Int J Mol Sci. 2023; 24(7). PMC: 10094085. DOI: 10.3390/ijms24076372. View

11.

da Silva J, Rodrigues F, Gomes de Mesquita G, Fernandes P, Thuler L, de Melo A . Triple-Negative Breast Cancer: Assessing the Role of Immunohistochemical Biomarkers on Neoadjuvant Treatment. Breast Cancer (Dove Med Press). 2021; 13:31-44. PMC: 7810824. DOI: 10.2147/BCTT.S287320. View

12.

Azadnajafabad S, Moghaddam S, Mohammadi E, Delazar S, Rashedi S, Baradaran H . Patterns of better breast cancer care in countries with higher human development index and healthcare expenditure: Insights from GLOBOCAN 2020. Front Public Health. 2023; 11:1137286. PMC: 10130425. DOI: 10.3389/fpubh.2023.1137286. View

13.

Ghorbanzadeh V, Mohammadi M, Dariushnejad H, Abhari A, Chodari L, Mohaddes G . Cardioprotective Effect of Crocin Combined with Voluntary Exercise in Rat: Role of Mir-126 and Mir-210 in Heart Angiogenesis. Arq Bras Cardiol. 2017; 109(1):54-62. PMC: 5524476. DOI: 10.5935/abc.20170087. View

14.

Aban C, Lombardi A, Neiman G, Biani M, La Greca A, Waisman A . Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT. Sci Rep. 2021; 11(1):2048. PMC: 7820496. DOI: 10.1038/s41598-021-81735-1. View

15.

Arzi L, Farahi A, Jafarzadeh N, Riazi G, Sadeghizadeh M, Hoshyar R . Inhibitory Effect of Crocin on Metastasis of Triple-Negative Breast Cancer by Interfering with Wnt/β-Catenin Pathway in Murine Model. DNA Cell Biol. 2018; 37(12):1068-1075. DOI: 10.1089/dna.2018.4351. View

16.

Arzi L, Hoshyar R . Saffron anti-metastatic properties, ancient spice novel application. Crit Rev Food Sci Nutr. 2021; 62(14):3939-3950. DOI: 10.1080/10408398.2020.1871320. View

17.

Majidpoor J, Mortezaee K . Steps in metastasis: an updated review. Med Oncol. 2021; 38(1):3. DOI: 10.1007/s12032-020-01447-w. View

18.

Dass S, Tan K, Selva Rajan R, Mokhtar N, Mohd Adzmi E, Wan Abdul Rahman W . Triple Negative Breast Cancer: A Review of Present and Future Diagnostic Modalities. Medicina (Kaunas). 2021; 57(1). PMC: 7826673. DOI: 10.3390/medicina57010062. View

19.

Wu T, Chen H, Shyur L . Current Advancements of Plant-Derived Agents for Triple-Negative Breast Cancer Therapy through Deregulating Cancer Cell Functions and Reprogramming Tumor Microenvironment. Int J Mol Sci. 2021; 22(24). PMC: 8703661. DOI: 10.3390/ijms222413571. View

20.

Ma W, Xie Z, Chen H, Zeng L, Chen X, Feng S . Nuclear translocation of β-catenin induced by E-cadherin endocytosis causes recurrent erosion of diabetic cornea. Exp Biol Med (Maywood). 2021; 246(10):1167-1176. PMC: 8142105. DOI: 10.1177/1535370220983243. View