Crucifera sulforaphane (SFN) inhibits the growth of nasopharyngeal carcinoma through DNA methyltransferase 1 (DNMT1)/Wnt inhibitory factor 1 (WIF1) axis

Autor: Roger Kai Cheong Ngan, Nai Ki Mak, George S.W. Tsao, Hong Lok Lung, Anne Wing Mui Lee, Wai Tong Ng, Timothy Tak Chun Yip, LS Chan, Kwok Wai Lo, Maria Li Lung, Jonathan W C Wong, Luo Chen
Rok vydání: 2018
Předmět:
DNA (Cytosine-5-)-Methyltransferase 1
Male
Small interfering RNA
Population
Cell
Pharmaceutical Science
Mice
Nude
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
SOX2
Cancer stem cell
Isothiocyanates
Cell Line
Tumor
Drug Discovery
Antineoplastic Combined Chemotherapy Protocols
otorhinolaryngologic diseases
medicine
Animals
Humans
education
030304 developmental biology
Adaptor Proteins
Signal Transducing
Pharmacology
0303 health sciences
education.field_of_study
Mice
Inbred BALB C
Nasopharyngeal Carcinoma
SOXB1 Transcription Factors
Wnt signaling pathway
Nasopharyngeal Neoplasms
medicine.disease
Antineoplastic Agents
Phytogenic
Xenograft Model Antitumor Assays
stomatognathic diseases
medicine.anatomical_structure
Complementary and alternative medicine
chemistry
Nasopharyngeal carcinoma
030220 oncology & carcinogenesis
Sulfoxides
Brassicaceae
Cancer research
Neoplastic Stem Cells
Molecular Medicine
Cisplatin
Sulforaphane
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology. 63
ISSN: 1618-095X
Popis: 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.
Databáze: OpenAIRE
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