title: Salinomycin possesses anti-tumor activity and inhibits breast cancer stem-like cells via an apoptosis-independent pathway.
abstract: Cancer stem cells (CSCs) play important roles in the formation, growth and recurrence of tumors, particularly following therapeutic intervention. Salinomycin has received recent attention for its ability to target breast cancer stem cells (BCSCs), but the mechanisms of action involved are not fully understood. In the present study, we sought to investigate the mechanisms responsible for salinomycin's selective targeting of BCSCs and its anti-tumor activity. Salinomycin suppressed cell viability, concomitant with the downregulation of cyclin D1 and increased p27(kip1) nuclear accumulation. Mammosphere formation assays revealed that salinomycin suppresses self-renewal of ALDH1-positive BCSCs and downregulates the transcription factors Nanog, Oct4 and Sox2. TUNEL analysis of MDA-MB-231-derived xenografts revealed that salinomycin administration elicited a significant reduction in tumor growth with a marked downregulation of ALDH1 and CD44 levels, but seemingly without the induction of apoptosis. Our findings shed further light on the mechanisms responsible for salinomycin's effects on BCSCs.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Hyunsook
authors.initials: H
authors.lastname: An
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Nahyun
authors.initials: N
authors.lastname: Lee
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Youngkwan
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea.
authors.forename: Eunhye
authors.initials: E
authors.lastname: Oh
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. Electronic address: cancer@korea.ac.kr.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seo
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011714:Pyrans / Q000494:pharmacology*; D050697:Retinal Dehydrogenase / Q000037:antagonists & inhibitors; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000095662:Polyether Polyketides
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; D000970:Antineoplastic Agents; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D011714:Pyrans; D050697:Retinal Dehydrogenase; D014157:Transcription Factors; C530104:CCND1 protein, human; C497483:CD44 protein, human; C436291:CDKN1B protein, human; C010327:salinomycin; D000095662:Polyether Polyketides; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse
keywords: ALDH1; Breast cancer stem cells; Mammosphere; Salinomycin