Deamino-hydroxy-phoslactomycin B, a biosynthetic precursor of phoslactomycin, induces myeloid differentiation in HL-60 cells |
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| Authors: | Siro Simizu Toshihiko Nogawa Masashi Ueki Yuichi Kobayashi |
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| Institution: | a Antibiotics Laboratory and Chemical Biology Department, Advanced Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
b Department of Biomolecular Engineering, Tokyo Institute of Technology, Box B52, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan |
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| Abstract: | 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)2D3 induced retinoic acid receptor-β and 1α, 25(OH)2 D3 24-hydroxylase, respectively, whereas HPLM did not, suggesting that HPLM is a novel differentiation inducer. |
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| Keywords: | Differentiation Phoslactomycin Protein phosphatase 2A HL-60 Natural product All-trans retinoic acid Cell cycle Vitamin D3 Acute myeloid leukemia |
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