title: Induction of necrosis in human myeloma cells by kigamicin.
abstract: BACKGROUND
  Kigamicin (KGM) is a novel compound derived from Actinomycetes that was originally reported to induce necrosis in pancreatic cancer cells only under nutrient-starved conditions via inhibition of PI3-kinase. The effects of KGM on myeloma cells were investigated.
  
  
  METHODS
  Cytotoxic activity was quantified using WST8 assay. Necrosis was determined by Annexin V/PI staining. Regulatory protein levels were assessed by Western blot. LY294002 was utilized as a PI3-kinase inhibitor.
  
  
  RESULTS
  KGM induced necrosis in myeloma cells in nutrient rich conditions with a CC50 of approximately 100 nM. KGM did not induce necrosis in normal lymphocytes. Cyclin D1, p21, p-AKT and p-ERK were inhibited by KGM while LY294002 did not inhibit cell death by KGM. A melphalan-resistant myeloma cell line was more susceptible to KGM than the melphalan-sensitive parental cell line.
  
  
  CONCLUSIONS
  KGM-induced necrosis in myeloma cells even at very low concentration. The present data warrant further investigation into the use of KGM as a potential therapeutic agent for multiple myeloma.
authors.affiliation: Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Esumi
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hata
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D010080:Oxazoles / Q000494:pharmacology*; D010766:Phosphorylation
chemical_list: D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; D010080:Oxazoles; C484116:kigamicin A; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases