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Yokogi S, Tsubota T, Kanki K, et al. Wnt/Beta-Catenin Signal Inhibitor HC-1 Sensitizes Oral Squamous Cell Carcinoma Cells to 5-Fluorouracil through Reduction of CD44-Positive Population. Yonago Acta Med. 2016;59(2):93-9
Yokogi, S., Tsubota, T., Kanki, K., Azumi, J., Itaba, N., Oka, H., Morimoto, M., Ryoke, K., & Shiota, G. (2016). Wnt/Beta-Catenin Signal Inhibitor HC-1 Sensitizes Oral Squamous Cell Carcinoma Cells to 5-Fluorouracil through Reduction of CD44-Positive Population. Yonago acta medica, 59(2), 93-9.
Yokogi, Satoshi, et al. "Wnt/Beta-Catenin Signal Inhibitor HC-1 Sensitizes Oral Squamous Cell Carcinoma Cells to 5-Fluorouracil through Reduction of CD44-Positive Population." Yonago acta medica vol. 59,2 (2016): 93-9.
Yokogi S, Tsubota T, Kanki K, Azumi J, Itaba N, Oka H, Morimoto M, Ryoke K, Shiota G. Wnt/Beta-Catenin Signal Inhibitor HC-1 Sensitizes Oral Squamous Cell Carcinoma Cells to 5-Fluorouracil through Reduction of CD44-Positive Population. Yonago Acta Med. 2016 Jun 29;59(2):93-9. eCollection 2016 Jun. PMID: 27493479; PMCID: PMC4973014.
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Yonago Acta Med. 2016 Jun 29;59(2):93-9. eCollection 2016 Jun.

Wnt/Beta-Catenin Signal Inhibitor HC-1 Sensitizes Oral Squamous Cell Carcinoma Cells to 5-Fluorouracil through Reduction of CD44-Positive Population.

Yonago acta medica

Satoshi Yokogi, Toshiaki Tsubota, Keita Kanki, Junya Azumi, Noriko Itaba, Hiroyuki Oka, Minoru Morimoto, Kazuo Ryoke, Goshi Shiota

Affiliations

  1. Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan; †Division of Oral and Maxillofacial Biopathological Surgery, Department of Medicine of Sensory and Motor Organs, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
  2. Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
  3. ‡Department of Biomedical Engineering, Faculty of Engineering, Okayama University of Science, Okayama 700-0005, Japan.
  4. §Division of Instrumental Analysis, Research Center for Bioscience and Technology, Tottori University, Tottori 680-8550, Japan.
  5. †Division of Oral and Maxillofacial Biopathological Surgery, Department of Medicine of Sensory and Motor Organs, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.

PMID: 27493479 PMCID: PMC4973014

Abstract

BACKGROUND: Oral squamous cell carcinoma is a prevalent and frequently lethal malignancy worldwide. Existence of treatment-resistant cancer stem cells is considered to be associated with tumor formation, recurrence and metastasis. Wnt/beta-catenin signal is one of the crucial signaling pathways for cancer stem cells. Wnt/beta-catenin signal inhibitor may reduce the population of cancer stem cells and improve therapeutic effects on the cancers.

METHODS: The effects of three derivatives of Wnt/beta-catenin signal inhibitors, HC-1, IC-2 and PN3-13, which we recently developed, on oral squamous cell carcinoma cell line HSC2, were examined by luciferase reporter assay, WST assay, cell sorting assay and apoptosis assay.

RESULTS: The reporter assay showed that these small molecule compounds reduced Wnt/beta-catenin transcriptional activity in HSC2 cells. Of these compounds, IC-2 and PN3-13 inhibited cell viability in a dose-dependent manner, whereas HC-1 did not at even higher concentrations. Notably, however, the cell-sorting assay revealed that HC-1 significantly reduces the CD44-positive population of oral squamous cell carcinoma cells, compared to other compounds without affecting cell viability. In addition, HC-1 increases the cytotoxicity of HSC2 cells to 5-fluorouracil. The combination treatment of HC-1 with 5-fluorouracil significantly increased the apoptotic cells whereas treatment by either compound did not.

CONCLUSION: These data suggest that HC-1 is an effective compound to target cancer stem cells, and the combination treatment of HC-1 and 5-fluorouracil can stimulate the tumor suppressive effect on oral squamous cell carcinoma cells.

Keywords: 5-fluorouracil; Wnt/beta-catenin signal inhibitor; cancer stem cells; oral squamous cell carcinoma; small molecule compound

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