Toxicological Research

  • 제25권4호
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  • Pages.181-188
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  • 2009
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
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Cytotoxic Effects on HL-60 Cells of Myosin Light Chain Kinase Inhibitor ML-7 Alone and in Combination with Flavonoids

  • Lee, Joong-Won (School of Public Health and Institute of Health and Environment, Seoul National University) ;
  • Kim, Yang-Jee (School of Public Health and Institute of Health and Environment, Seoul National University) ;
  • Choi, Young-Joo (School of Public Health and Institute of Health and Environment, Seoul National University) ;
  • Woo, Hae-Dong (School of Public Health and Institute of Health and Environment, Seoul National University) ;
  • Kim, Gye-Eun (School of Public Health and Institute of Health and Environment, Seoul National University) ;
  • Ha, Tae-Kyung (School of Public Health and Institute of Health and Environment, Seoul National University) ;
  • Lee, Young-Hyun (School of Public Health and Institute of Health and Environment, Seoul National University) ;
  • Chung, Hai-Won (School of Public Health and Institute of Health and Environment, Seoul National University)
  • 발행 : 2009.12.01
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초록

Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p<0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with $40{\mu}M$ ML-7 for 2h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

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참고문헌

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