Effect of Cinnamic acid and FOLFOX in diminishing side population and downregulating cancer stem cell markers in colon cancer cell line HT-29

Abstract

Purpose

There is a lot of evidence suggesting that a small subset of cancer cells resistant to conventional chemotherapy and radiotherapy and known as cancer stem cells (CSCs) is responsible for promoting metastasis and cancer relapse. Therefore, targeting and eliminating the CSCs could lead to higher survival rates and a better quality of life. In comparison with conventional chemical drugs that may not be effective against CSCs, phytochemicals are strong anti-CSCs agents. The current study examines the effect of 5-fluorouracil plus oxaliplatin (FOLFOX) as a common chemotherapy drug on colorectal cancer as well as the influence of Cinnamic acid (CINN) as a plant-derived phytochemical on colon cancer stem-like cells in HT-29 adenocarcinoma cell line.

Methods

The anti-proliferative effect of FOLFOX and CINN was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Flow cytometry analysis was used for the identification of side population (SP), CD44, and CD133 positive cells. The expression of OCT4, NANOG, ABCB1, and ALDH1A was assessed by RT-PCR.

Results

The FOLFOX and CINN decreased cell viability in certain drug concentrations: IC50 = 5,40 μM oxaliplatin +220 μM 5-fluorouracil, and 13,50 mM for CINN. The CSC-associated markers (OCT4, NANOG, ABCB1, and ALDH1A) and the proportion of cancer stem-like cells (SP cells, CD44, and CD133 positive cells) were downregulated following the treatment of HT-29 adenocarcinoma cell line with IC50 concentrations of FOLFOX and CINN.

Conclusion

Our data suggests that CINN, a naturally occurring component, could be more effective than FOLFOX treatment in reducing the cancer stem-like cells and expression of CSC markers from HT-29 colon cancer cells.

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Acknowledgements

The authors thank Saeed Esmaeili Mahani at Department of Biology, Faculty of science, Shahid Bahonar University of Kerman for providing experimental equipment, Vice Chancellor for Research, Kerman University of Medical Science, Kerman, Iran for financial support.

Funding

This study was funded by Kerman University of Medical Science, Kerman, Iran (grant number: 96000157).

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Correspondence to Behjat Kalantari Khandani.

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

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Soltanian, S., Riahirad, H., Pabarja, A. et al. Effect of Cinnamic acid and FOLFOX in diminishing side population and downregulating cancer stem cell markers in colon cancer cell line HT-29. DARU J Pharm Sci 26, 19–29 (2018). https://doi.org/10.1007/s40199-018-0210-8

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Keywords

  • Colon cancer stem cells
  • Side population
  • Cinnamic acid
  • FOLFOX
  • Cancer stem cell markers