Salinomycin Abolished STAT3 and STAT1 Interactions and Reduced Telomerase Activity in Colorectal Cancer Cells.
Colorectal cancer is the third leading cause of cancer-related mortality in most developed countries. This mortality is mainly due to the metastatic progression to the liver with frequent recurrence. Colorectal cancer remains a therapeutic challenge and this has intensified the search for new drug targets. In an effort to establish a novel targeted-therapy, we studied the molecular mechanisms of cancer stem cell inhibitor salinomycin.



Co-immunoprecipitation was performed to examine STAT3-STAT1 protein interactions. Telomerase activity was measured by polymerase chain reaction (PCR) and ELISA assays. Apoptosis and cell stress arrays were analyzed to identify key proteins responding to salinomycin treatments.



IL-6 and TNF-α induced STAT3 and STAT1 interactions, however the interactions were abolished by salinomycin challenge. Salinomycin reduced cancer stem cell phenotype and decreased telomerase activity of colorectal cancer cells.



Our work uncovers a new mechanism through which salinomycin inhibits cancer stemness suggesting a novel targeted-therapy for metastatic colorectal cancer.
Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A. seyungchung@cdrewu.edu jayvadgama@cdrewu.edu jvadgama@ucla.edu.|Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.|David Geffen UCLA School of Medicine, Los Angeles, CA, U.S.A.
Seyung S
SS
Chung
Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A.|Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.
Debbie
D
Adekoya
Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A.|Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.
Ikechukwu
I
Enenmoh
Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A.|Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.
Orette
O
Clarke
Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A.|Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.|David Geffen UCLA School of Medicine, Los Angeles, CA, U.S.A.
Piwen
P
Wang
Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A.|Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.|David Geffen UCLA School of Medicine, Los Angeles, CA, U.S.A.
Marianna
M
Sarkyssian
Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A.|Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.|David Geffen UCLA School of Medicine, Los Angeles, CA, U.S.A.
Yong
Y
Wu
Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A. seyungchung@cdrewu.edu jayvadgama@cdrewu.edu jvadgama@ucla.edu.|Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A.|David Geffen UCLA School of Medicine, Los Angeles, CA, U.S.A.|Jonsson Comprehensive Cancer Center, Los Angeles, CA, U.S.A.
Jaydutt V
JV
Vadgama
D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition; D019073:HT29 Cells; D006801:Humans; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000494:pharmacology; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011714:Pyrans / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051176:beta Catenin / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D000095662:Polyether Polyketides
D001549:Benzamides; D015850:Interleukin-6; D011714:Pyrans; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D019098:Telomerase; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D048051:p38 Mitogen-Activated Protein Kinases; C495270:CTNNB1 protein, human; C470197:MST 312; C494079:STAT1 protein, human; C494086:STAT3 protein, human; C010327:salinomycin; D000095662:Polyether Polyketides
Cancer stem cells; MST-312; STAT1; STAT3; salinomycin; telomerase