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Silibinin suppresses the maintenance of colorectal cancer stem‐like cells by inhibiting PP2A/AKT/mTOR pathways
Author(s) -
Wang JirYou,
Chang ChiaChi,
Chiang ChaoChing,
Chen WeiMing,
Hung ShihChieh
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24043
Subject(s) - silibinin , pi3k/akt/mtor pathway , protein kinase b , cancer research , chemistry , flow cytometry , biology , signal transduction , immunology , biochemistry
Silibinin, an effective chemo‐preventive agent in various cancer types, suppresses cancer cell growth, but its effects on cancer stem‐like cells (CSLCs) remain unclear. This study aimed to examine whether silibinin inhibited the development of CSLCs and disclose the underlying signaling. The colorectal cancer spheroid culture system was used for enriching CSLCs. The effects of silibinin on CSLCs were evaluated by counting sphere numbers, and calculating the percentage of CD133+ cells by flow cytometry and immunofluorescence both in the absence and presence of different concentrations of silibinin. The results showed the sphere number of CCS was 36 ± 9.6 after 15 days of CSLC enrichment in spheroid culture, and the percentage of CD133+ cells increased to 18 ± 6.4% compared to 3 ± 0.8% before enrichment. Treatment with silibinin reduced the sphere formation to 5 ± 3.3 and decreased the CD133+ percentage to 8 ± 2.3%. Interestingly, treatment of silibinin suppressed the activation of the AKT Ser473/mTOR pathway in spheroid culture through suppressing the activity of protein phosphatase 2Ac subunit (PP2Ac). In a xenograft tumor model, treatment with silibinin also inhibited tumor formation rate and tumor growth. Silibinin, which inhibits colon CSLCs self‐renewal and sphere formation by suppressing the PP2Ac/AKT Ser473/mTOR pathway, may be a compound for developing new strategies in modulating CSLCs in cancer therapy. J. Cell. Biochem. 113: 1733–1743, 2012. © 2012 Wiley Periodicals, Inc.