Salinomycin can effectively kill ALDH(high) stem-like cells on gastric cancer

Biomed Pharmacother. 2011 Oct;65(7):509-15. doi: 10.1016/j.biopha.2011.06.006. Epub 2011 Aug 27.

Abstract

Salinomycin is a novel identified cancer stem cells (CSCs) killer. Higher ALDH activity represents CSCs characterization. Here, we screened ALDH activities on several gastric cancer cell lines and divided them into ALDH(high) and ALDH(low) gastric cancer groups. ALDH(high) cancer cells (NCI-N87 and SNU-1) disclosed more CSCs characteristics, such as higher levels of Sox2, Nanog and Nestin, more floating spheroid bodies, more colony formation and more resistance to conventional chemotherapeutic drugs 5-Fu and CDDP, compared to these parameters observed in ALDH(low) cancer cells (P<0.01). Importantly, ALDH(high) cancer cells are relatively sensitive to salinomycin when compared to ALDH(low) cancer cells (P<0.01). Our results confirmed ALDH as functional marker of CSCs population on gastric cancer. Salinomycin might be selective therapy for CSCs fraction, which is resistant to conventional anticancer drugs 5-Fu and CDDP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase / analysis*
  • Aldehyde Dehydrogenase / biosynthesis
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase 1 Family
  • Antibiotics, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents, Alkylating / pharmacology
  • Cisplatin / pharmacology
  • Enzyme Induction / drug effects
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Humans
  • Intermediate Filament Proteins / biosynthesis
  • Intermediate Filament Proteins / genetics
  • Nanog Homeobox Protein
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / enzymology
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nestin
  • Pyrans / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Retinal Dehydrogenase
  • SOXB1 Transcription Factors / biosynthesis
  • SOXB1 Transcription Factors / genetics
  • Spheroids, Cellular / drug effects
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology
  • Tumor Stem Cell Assay

Substances

  • Antibiotics, Antineoplastic
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Homeodomain Proteins
  • Intermediate Filament Proteins
  • NANOG protein, human
  • NES protein, human
  • Nanog Homeobox Protein
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Nestin
  • Pyrans
  • RNA, Messenger
  • RNA, Neoplasm
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • salinomycin
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase
  • Cisplatin
  • Fluorouracil