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Inhibitory effects of polymethoxyflavones on colon cancer stem cells
Author(s) -
Xu Fei,
Charoensinphon Noppawat,
Zheng Jinkai,
Xiao Hang
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb420
Subject(s) - cancer stem cell , aldehyde dehydrogenase , colorectal cancer , inhibitory postsynaptic potential , cancer research , chemistry , cancer cell , stem cell , cancer , biochemistry , enzyme , biology , medicine , endocrinology , microbiology and biotechnology
Increasing evidence suggests cancer stem cells (CSCs) may be responsible for occurrence of malignant tumors. Our previous studies showed that 5‐hydroxylnobiletin (5HN), a polymethoxyflavone found in citrus fruits had potent inhibitory effects on cancer cells, and 5HN was metabolized to 5,3′‐dihydroxylnobiletin (M1), 5,4′‐dihydroxylnobiletin (M2) and 5,3′4′‐trihydroxylnobiletin (M3) in rodents. Herein, we investigated the inhibitory effects of 5HN and its metabolites on human colon cancer stem cells. CSCs‐associated tumor spheres were obtained from human colon cancer cells. 5HN and its metabolites showed potent inhibition on the formation of both first and second generation tumor spheres. The inhibitory effects of M1 and M2 were similar to those of 5HN, while M3 showed much stronger activities than 5HN. For example, 5HN at 12.5 μM caused 70% inhibition on tumor sphere formation of HCT116 cells, while M3 at only 0.2 μM resulted in similar magnitude of inhibition. Overexpression of aldehyde dehydrogenase (ALDH) was considered as one of marker for stemness of CSCs. We quantified ALDH+ colon cancer cells after the treatments with 5HN and M3, and found that 5HN and M3 at 25 μM and 5 μM caused 60% and 40% inhibition on the abundance of ALDH+ cells, respectively. Overall, our study for the first time demonstrated the inhibitory effects of 5HN and its metabolites, especially M3 on human colon CSCs.