Salinomycin selectively targets 'CD133+' cell subpopulations and decreases malignant traits in colorectal cancer lines.
BACKGROUND
Cancer stem-like cells (CSCs) in colorectal cancers (CRC) may account for the failure of treatments because they are resistant to many current anticancer therapies. Salinomycin, a potassium ionophore, was recently identified as a selective inhibitor of breast CSCs.


METHODS
The human CRC cell lines HT29 and SW480 were treated with salinomycin and oxaliplatin. Cell viability was determined with cell counting kit 8. Fraction of CD133+ cell subpopulations was assessed by Flow Cytometric analysis. Clonogenecity and migration were determined with soft agar and Boyden chamber assays. Molecular changes were assessed by immunofluorescence staining, RT-PCR, and Western blot analysis.


RESULTS
We report that salinomycin reduces the proportion of CD133+ subpopulations in human CRC HT29 and SW480 cells. Furthermore, salinomycin treatment decreases colony-forming ability and cell motility in HT29 cells. Moreover, salinomycin downregulates the expression of vimentin and induces the E-cadherin expression in HT29 cells.


CONCLUSIONS
This study demonstrates the ability of salinomycin to selectively target "CD133+" cell subpopulations and decrease the malignant traits in colorectal cancer lines.
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Tao-Tao
TT
Dong
Hou-Min
HM
Zhou
Lin-Lin
LL
Wang
Bo
B
Feng
Bo
B
Lv
Min-Hua
MH
Zheng
D000071916:AC133 Antigen; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011714:Pyrans / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000095662:Polyether Polyketides
D000071916:AC133 Antigen; D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D000970:Antineoplastic Agents; D015820:Cadherins; D006023:Glycoproteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010455:Peptides; D011714:Pyrans; D012333:RNA, Messenger; C000606023:PROM1 protein, human; C010327:salinomycin; D000095662:Polyether Polyketides