Seyung S Chung1,2,3, Debbie Adekoya4,2, Ikechukwu Enenmoh4,2, Orette Clarke4,2, Piwen Wang4,2,3, Marianna Sarkyssian4,2,3, Yong Wu4,2,3, Jaydutt V Vadgama1,2,3,5. 1. 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. 2. Charles R. Drew University of Medicine and Science, Los Angeles, CA, U.S.A. 3. David Geffen UCLA School of Medicine, Los Angeles, CA, U.S.A. 4. Department of Internal Medicine, Division of Cancer Research and Training, Los Angeles, CA, U.S.A. 5. Jonsson Comprehensive Cancer Center, Los Angeles, CA, U.S.A.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Our work uncovers a new mechanism through which salinomycin inhibits cancer stemness suggesting a novel targeted-therapy for metastatic colorectal cancer. Copyright
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Our work uncovers a new mechanism through which salinomycin inhibits cancer stemness suggesting a novel targeted-therapy for metastatic colorectal cancer. Copyright
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