Document Type

Journal Article

Department/Unit

Department of Biology

Language

English

Abstract

Background

Sulforaphane (SFN), a natural compound present in cruciferous vegetable, has been shown to possess anti-cancer activities. Cancer stem cell (CSC) in bulk tumor is generally considered as treatment resistant cell and involved in cancer recurrence. The effects of SFN on nasopharyngeal carcinoma (NPC) CSCs have not yet been explored.

Purpose

The present study aims to examine the anti-tumor activities of SFN on NPC cells with CSC-like properties and the underlying mechanisms.

Methods

NPC cells growing in monolayer culture, CSCs-enriched NPC tumor spheres, and also the NPC nude mice xenograft were used to study the anti-tumor activities of SFN on NPC. The population of cells expressing CSC-associated markers was evaluated using flow cytometry and aldehyde dehydrogenase (ALDH) activity assay. The effect of DNA methyltransferase 1 (DNMT1) on the growth of NPC cells was analyzed by using small interfering RNA (siRNA)-mediated silencing method.

Results

SFN was found to inhibit the formation of CSC-enriched NPC tumor spheres and reduce the population of cells with CSC-associated properties (SRY (Sex determining Region Y)-box 2 (SOX2) and ALDH). In the functional study, SFN was found to restore the expression of Wnt inhibitory factor 1 (WIF1) and the effect was accompanied with the downregulation of DNMT1. The functional activities of WIF1 and DNMT1 were confirmed using exogenously added recombinant WIF1 and siRNA knockdown of DNMT1. Moreover, SFN was found to inhibit the in vivo growth of C666-1 cells and enhance the anti-tumor effects of cisplatin.

Conclusion

Taken together, we demonstrated that SFN could suppress the growth of NPC cells via the DNMT1/WIF1 axis.

Keywords

Sulforaphane, Nasopharyngeal carcinoma, DNMT1, WIF1

Publication Date

10-2019

Source Publication Title

Phytomedicine

Volume

63

Publisher

Elsevier

DOI

10.1016/j.phymed.2019.153058

Link to Publisher's Edition

http://dx.doi.org/10.1016/j.phymed.2019.153058

ISSN (print)

09447113

ISSN (electronic)

1618095X

Available for download on Sunday, November 01, 2020

Included in

Biology Commons

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