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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2017

Open Access 01-12-2017 | Research

Sulfasalazine attenuates evading anticancer response of CD133-positive hepatocellular carcinoma cells

Authors: Yeonhwa Song, Jaewoo Jang, Tae-Hoon Shin, Sang Mun Bae, Jin-sun Kim, Kang Mo Kim, Seung-Jae Myung, Eun Kyung Choi, Haeng Ran Seo

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

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Abstract

Background

CD133-positive cells in hepatocellular carcinoma (HCC) exhibit cancer stem cell (CSC)-like properties as well as resistance to chemotherapeutic agents and ionizing radiation; however, their function remains unknown. In this paper, we identified a hitherto unknown mechanism to overcome CD133-induced resistance to anticancer therapy.

Methods

We applied an alternative approach to enrich the CD133-positive HCC population by manipulating 3D culture conditions. Defense mechanisms against reactive oxygen species (ROS) in CSC spheroids were evaluated by fluorescence image-based phenotypic screening system. Further, we studied the effect of sulfasalazine on ROS defense system and synergistic therapeutic efficacy of anticancer therapies both in culture and in vivo HCC xenograft mouse model.

Results

Here, we found that oxidative stress increase CD133 expression in HCC and increased CD133 expression enhanced the capacity of the defense system against ROS, and thereby play a central role in resistance to liver cancer therapy. Moreover, ablation of CD133 attenuated not only the capacity for defense against ROS, but also chemoresistance, in HCC through decreasing glutathione (GSH) levels in vitro. Sulfasalazine, a potent xCT inhibitor that plays an important role in maintaining GSH levels, impaired the ROS defense system and increased the therapeutic efficacy of anticancer therapies in CD133-positive HCC but not CD133-negative HCC in vivo and in vitro.

Conclusion

These results strongly indicate functional roles for CD133 in ROS defense and in evading anticancer therapies in HCC, and suggest that sulfasalazine, administered in combination with conventional chemotherapy, might be an effective strategy against CD133-positive HCC cells.

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Metadata
Title
Sulfasalazine attenuates evading anticancer response of CD133-positive hepatocellular carcinoma cells
Authors
Yeonhwa Song
Jaewoo Jang
Tae-Hoon Shin
Sang Mun Bae
Jin-sun Kim
Kang Mo Kim
Seung-Jae Myung
Eun Kyung Choi
Haeng Ran Seo
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-017-0511-7

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