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Suppressive role of Viola odorata extract on malignant characters of mammosphere-derived breast cancer stem cells

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Abstract

Background

Mammospheres are breast cancer stem cells (BCSCs) that could be yielded through culturing cells in non-adherent and non-differentiating condition. With regard to therapy resistance of cancer stem cells (CSCs), it is essential to discover efficient approaches targeting CSCs. Viola odorata extract has been considered as a traditional herbal anti-metastatic drug in several cancer cells. Effect of this drug on BCSCs has not been clearly identified. Current study tries to detect and to compare effect of Viola odorata extract on malignant characterization of breast cancer cell lines and BCSCs.

Materials and methods

MCF7 and SKBR3 and their derived mammospheres as BCSCs were used and the effect of alcoholic extraction of Viola odorata on apoptosis and malignant characters of MCF7, SKBR3 and their derived BCSCs were analyzed and compared.

Results

Viola odorata extract induced cell death in MCF7, SKBR3 and their derived mammospheres through apoptosis without any effects on MCF10A. Also, this extract showed anti-migratory, anti-invasion and anti-colony formation activity in MCF7, SKBR3 and their derived mammospheres which was significantly more in MCF7- and SKBR3-derived mammospheres. Also, this extract decreased size and volume of tumors generated by MCF7, SKBR3 and their derived mammospheres in chicken embryo model.

Conclusion

Viola odorata extract exerted anti-cancerous activity on both breast cancer cell lines and their derived BCSCs. Anti-cancerous activity of this extract was significantly more in MCF7-, SKBR3-derived mammospheres in comparison with dedicated cell lines. Data suggest that Viola odorata extract mostly targets cancerous cells, not normal cells with exception in high concentration. It acts in a cell-dependent manner.

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Abbreviations

ALDH:

Aldehyde dehydrogenase

b-FGF:

Basic fibroblast growth factor

BCSCs:

Breast cancer stem cells

CSCs:

Cancer stem cells

CAM:

Chorioallantoic membrane

Dox:

Doxorubicin

DMEM/F12:

Dulbecco’s modified Eagle’s medium/F12

EGF:

Epidermal growth factor

EGCG:

Epigallocatechin gallate

ESA:

Epithelial-specific antigen

ER:

Estrogen receptor

ECM:

Extracellular matrix

FBS:

Fetal bovine serum

H&E staining:

Hematoxylin and eosin staining

HPLC:

High-performance liquid chromatography

HER2:

Human epidermal growth factor receptor 2

IHC:

Immunohistochemistry

IC50:

50% Inhibitory concentration

OSCC:

Oral squamous cell carcinoma

OS:

Osteosarcoma

PARP:

Poly ADP ribose polymerase

PR:

Progesterone receptor

TBMS1:

Tubeimoside-1

TICs:

Tumor-initiating cells

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Acknowledgements

We thank our great colleague Mr. Abbas Kiani Esfahani for his technical assistance on flow cytometry. Also, we thank Goldaru Company, for the gift-giving alcoholic Viola odorata extract.

Funding

This project was supported by the Goldaru company to approve the anti-cancerous effects of Viola odorata extract. This project was funded by a grant-in-aid of research from Iran National Science Foundation (Award no. 93021399) to K. G., as the Principal Investigator.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar Jerib Ave., Azadi Sq., 81746-73441, Isfahan, Iran

    S. Yousefnia & K. Ghaedi

  2. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Royan St., Salman St., Khorsagan, 816513-1378, Isfahan, Iran

    D. Naseri, F. Seyed Forootan, M. H. Nasr Esfahani & K. Ghaedi

  3. Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran

    F. Seyed Forootan

  4. Department of Surgery and Breast Cancer Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    M. Tabatabaeian

  5. Goldaru Pharmaceutical Company, Isfahan, Iran

    F. Moattar & T. Ghafghazi

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  1. S. Yousefnia
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  2. D. Naseri
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  4. M. Tabatabaeian
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  5. F. Moattar
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  8. K. Ghaedi
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Contributions

SY: designing research studies, conducting experiments, acquiring data, analyzing data, providing reagents, and writing the manuscript. DN: designing research studies, conducting experiments, data interpretation. FSF: designing research studies, data interpretation, manuscript writing, and final approval of the manuscript. MT: data interpretation, conducting experiments. FM: data interpretation, conducting experiments. TG: data interpretation, conducting experiments. MHNE: designing research studies, data interpretation, manuscript writing, and final approval of the manuscript. KG: designing research studies, data interpretation, manuscript writing, and final approval of the manuscript.

Corresponding authors

Correspondence to F. Seyed Forootan or K. Ghaedi.

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The permission to use chicken embryo based on the standard protocols was obtained by Ethics Committee of Royan Institute (The permission to use chick embryo based on the standard protocols was obtained by Ethics Committee of Royan Institute (Project no. IR ACECR ROYAN REC IR ACECR ROYAN REC).

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Yousefnia, S., Naseri, D., Seyed Forootan, F. et al. Suppressive role of Viola odorata extract on malignant characters of mammosphere-derived breast cancer stem cells . Clin Transl Oncol 22, 1619–1634 (2020). https://doi.org/10.1007/s12094-020-02307-9

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