Deamino-hydroxy-phoslactomycin B, a biosynthetic precursor of phoslactomycin, induces myeloid differentiation in HL-60 cells

• Published in: Biochemical and biophysical research communications Vol. 383; no. 4; pp. 406 - 410
• Main Authors: Simizu, Siro, Teruya, Takayuki, Nogawa, Toshihiko, Aono, Harumi, Ueki, Masashi, Uramoto, Masakazu, Kobayashi, Yuichi, Osada, Hiroyuki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.06.2009
• Subjects: Acute myeloid leukemia; All- trans retinoic acid; Cell cycle; Cell Differentiation; Differentiation; HL-60; HL-60 Cells; Humans; Lactones - metabolism; Myeloid Cells - cytology; Myeloid Cells - drug effects; Natural product; Organophosphorus Compounds - metabolism; Phoslactomycin; Protein Phosphatase 2 - antagonists & inhibitors; Protein phosphatase 2A; Pyrones - chemistry; Pyrones - metabolism; Pyrones - pharmacology; Streptomyces; Streptomyces - chemistry; Streptomyces - metabolism; Vitamin D 3; Vitamin D 3; Cell cycle; Natural product; HL-60; Differentiation; All- trans retinoic acid; Acute myeloid leukemia; Phoslactomycin; Protein phosphatase 2A
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.04.014

During the screening for novel differentiation inducers, we found that a culture broth of Streptomyces sp. HK-803 induced myeloid differentiation of HL-60 cells. The active substance was identified as deamino-hydroxy-phoslactomycin B (HPLM) by mass spectrometry, and synthesized HPLM also induced the differentiation of HL-60 cells. HPLM showed greater inhibition of protein phosphatase 2A (PP2A) activity than phoslactomycin B (PLMB); however, PLMB and okadaic acid did not induce differentiation. Moreover, treatment with ATRA and 1α, 25(OH) 2D 3 induced retinoic acid receptor-β and 1α, 25(OH) 2 D 3 24-hydroxylase, respectively, whereas HPLM did not, suggesting that HPLM is a novel differentiation inducer.