Deamino-hydroxy-phoslactomycin B, a biosynthetic precursor of phoslactomycin, induces myeloid differentiation in HL-60 cells.
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 1alpha, 25(OH)2D3 induced retinoic acid receptor-beta and 1alpha, 25(OH)2D3 24-hydroxylase, respectively, whereas HPLM did not, suggesting that HPLM is a novel differentiation inducer.
Antibiotics Laboratory and Chemical Biology Department, Advanced Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Siro
S
Simizu
Takayuki
T
Teruya
Toshihiko
T
Nogawa
Harumi
H
Aono
Masashi
M
Ueki
Masakazu
M
Uramoto
Yuichi
Y
Kobayashi
Hiroyuki
H
Osada
D002454:Cell Differentiation; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism
D007783:Lactones; D009943:Organophosphorus Compounds; D011753:Pyrones; C541020:deamino-hydroxy-phoslactomycin B; C060449:phoslactomycin B; D054648:Protein Phosphatase 2