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Volume 12
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10.3390/cancers12051193
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Article

Chromenopyrimidinone Controls Stemness and Malignancy by suppressing CD133 Expression in Hepatocellular Carcinoma

by
Yeonhwa Song
1,
Sanghwa Kim
1,
Hyeryon Lee
2,
Joo Hwan No
2,
Hyung Chul Ryu
3,
Jason Kim
3,
Jee Woong Lim
3,
Moonhee Kim
3,
Inhee Choi
4,* and
Haeng Ran Seo
1,*
1
Cancer Biology Laboratory, Institut Pasteur Korea, Seongnam-si 13488, Korea
2
Leishmania Research Laboratory, Institut Pasteur Korea, Seongnam-si 13488, Korea
3
R&D Center, J2H Biotech, Suwon-si 16648, Korea
4
Medicinal Chemistry, Institut Pasteur Korea, Seongnam-si 13488, Korea
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(5), 1193; https://doi.org/10.3390/cancers12051193
Submission received: 10 March 2020 / Revised: 17 April 2020 / Accepted: 24 April 2020 / Published: 8 May 2020
(This article belongs to the Special Issue Cancer Stem Cells and Therapy Resistance)
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Abstract

Hepatocellular carcinoma (HCC) is a highly malignant human cancer that has increasing mortality rates worldwide. Because CD133+ cells control tumor maintenance and progression, compounds that target CD133+ cancer cells could be effective in combating HCC. We found that the administration of chromenopyrimidinone (CPO) significantly decreased spheroid formation and the number of CD133+ cells in mixed HCC cell populations. CPO not only significantly inhibited cell proliferation in HCC cells exhibiting different CD133 expression levels, but also effectively induced apoptosis and increased the expression of LC3-II in HCC cells. CPO also exhibits in vivo therapeutic efficiency in HCC. Specifically, CPO suppressed the expression of CD133 by altering the subcellular localization of CD133 from the membrane to lysosomes in CD133+ HCC cells. Moreover, CPO treatment induced point mutations in the ADRB1, APOB, EGR2, and UBE2C genes and inhibited the expression of these proteins in HCC and the expression of UBE2C is particularly controlled by CD133 expression among those four proteins in HCC. Our results suggested that CPO may suppress stemness and malignancies in vivo and in vitro by decreasing CD133 and UBE2C expression in CD133+ HCC. Our study provides evidence that CPO could act as a novel therapeutic agent for the effective treatment of CD133+ HCC.
Keywords: liver cancer stem cells (LCSCs); CD133; hepatocellular carcinoma (HCC); UBE2C; chromenopyrimidinone (CPO) liver cancer stem cells (LCSCs); CD133; hepatocellular carcinoma (HCC); UBE2C; chromenopyrimidinone (CPO)

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MDPI and ACS Style

Song, Y.; Kim, S.; Lee, H.; No, J.H.; Ryu, H.C.; Kim, J.; Lim, J.W.; Kim, M.; Choi, I.; Seo, H.R. Chromenopyrimidinone Controls Stemness and Malignancy by suppressing CD133 Expression in Hepatocellular Carcinoma. Cancers 2020, 12, 1193. https://doi.org/10.3390/cancers12051193

AMA Style

Song Y, Kim S, Lee H, No JH, Ryu HC, Kim J, Lim JW, Kim M, Choi I, Seo HR. Chromenopyrimidinone Controls Stemness and Malignancy by suppressing CD133 Expression in Hepatocellular Carcinoma. Cancers. 2020; 12(5):1193. https://doi.org/10.3390/cancers12051193

Chicago/Turabian Style

Song, Yeonhwa, Sanghwa Kim, Hyeryon Lee, Joo Hwan No, Hyung Chul Ryu, Jason Kim, Jee Woong Lim, Moonhee Kim, Inhee Choi, and Haeng Ran Seo. 2020. "Chromenopyrimidinone Controls Stemness and Malignancy by suppressing CD133 Expression in Hepatocellular Carcinoma" Cancers 12, no. 5: 1193. https://doi.org/10.3390/cancers12051193

APA Style

Song, Y., Kim, S., Lee, H., No, J. H., Ryu, H. C., Kim, J., Lim, J. W., Kim, M., Choi, I., & Seo, H. R. (2020). Chromenopyrimidinone Controls Stemness and Malignancy by suppressing CD133 Expression in Hepatocellular Carcinoma. Cancers, 12(5), 1193. https://doi.org/10.3390/cancers12051193

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