Induction of necrosis in human myeloma cells by kigamicin.
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.
Nakamura
Miki
M
Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan.
Esumi
Hiroyasu
H
Jin
Lu
L
Mitsuya
Hiroaki
H
Hata
Hiroyuki
H
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
D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; D010080:Oxazoles; C484116:kigamicin A; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases