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. Materials and 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. Conclusion: 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.