Compound 278E, structurally modified from tanshinone, induces monocytic differentiation and regulates proto-oncogene expression in human leukemic HL-60 cells.
Tanshinone derivative compounds, isolated from Salvia miltiorrhiza Bunge (Labiatae), have been reported as microtubule inhibitors with antimitotic activity. In this study, we examined the growth-inhibiting and differentiation-inducing effect of these compounds on human leukemic HL-60 cells. The expression of protein kinase C (PKC) and proto-oncogenes in 278E-treated cells was also assessed. All tanshinone derivative compounds exhibited growth-inhibitory effects on HL-60 cells, but only 278E induced cell differentiation. Morphological observation of 278E-treated HL-60 cells showed a greater percentage of monocytes and macrophages (Mo/Mphi). Treatment with 5 microg/ml 278E resulted in a marked increase in the percentages of superoxide-producing (up to 95.5+/-1.8%) and non-specific esterase-positive cells (up to 80.3+/-9.1%). The differentiated cells also expressed cell surface antigens characteristic of Mo/Mphi, including CD11b, CD14 and CD68. Neither cellular changes in isozymes of PKC nor translocation of these isozymes from cytosol to cell membrane were seen in 278E-treated HL-60 cells. 278E caused a downregulation of c-myc as well as an up-regulation of c-fms, c-jun and c-fos.
Liao
Hui-Fen
HF
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
Shyu
Shin-Yi
SY
Kuo
Yueh-Hsiung
YH
Yang
Yuh-Cheng
YC
Chen
Yu-Jen
YJ
D045784:Abietanes; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D004950:Esterases / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010616:Phenanthrenes / Q000737:chemistry*; D011493:Protein Kinase C / Q000096:biosynthesis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D027561:Salvia miltiorrhiza; D013481:Superoxides / Q000378:metabolism
C503441:5-(3-hydroxypropyl)-7-methoxy-2-(3'-methoxy-4'-benzyloxyophenyl)-3-benzo(b)furan; D045784:Abietanes; D000970:Antineoplastic Agents; D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; C000715470:MAS1 protein, human; D010616:Phenanthrenes; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C021751:tanshinone; D013481:Superoxides; D011493:Protein Kinase C; D004950:Esterases