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Extract of Listeria monocytogenes Induces the Apoptosis on the Human Promyelocytic Leukemia Cells, HL-60 Cells

Listeria monocytogenes에 의해 HL-60 cell의 세포고사 유도 효과 규명

  • 양은주 (대구한의대학교 보건치료대학 임상병리학과) ;
  • 김동현 (부산가톨릭대학교 보건과학대학 방사선학과) ;
  • 장정현 (대구한의대학교 보건치료대학 임상병리학과)
  • Received : 2011.10.28
  • Accepted : 2011.11.24
  • Published : 2012.02.28

Abstract

Acute promyelocytic leukemia (APL) is a cancer of the blood and bone marrow. Although all-trans retionic acid (ATRA) is the agents for ALP therapy, there are various side effects. For overcome this problem, we need the development of new therapeutic agents for APL. A number of bacteria produce various virulence factors with cytotoxic effects on human cancer cells. To understand the anti-cancer effect of Listeria monocytogenes on APL, we examined alteration of the cell viability, apoptosis and cell cycle arrest of the human promyelocytic leukemia cell line, HL-60 cells. The cell supernatant (LmSup) and the extract of L. monocytogenes (LmE) inhibited the cell viability and induced apoptosis of HL-60 cells. These cytotoxic effect of LmSup and LmE mediated by modulation of cell cycle and ROS production. These results indicate that released or included bacterial molecules from L. monocytogenes have a cytotoxicity in HL-60 cells. Therefore, LmSup and LmE may be used as the potential target for the treatment of cancer induced by HL-60 cells.

급성 전골수구성 백혈병(acute promyelocytic leukemia, APL)은 치료제가 한정적이고 그 또한 다양한 부작용을 초래한다. 최근 암세포 형성 억제에 세균 추출물을 사용하는 경우가 증가하는데 이를 이용하여 기존의 약제보다 효과적이면서 부작용이 적은 치료제 개발이 필요하다. 본 연구에서는 L. monocytogenes에서 분비되는 물질(LmSup)과 세균 자체가 함유하고 있는 물질(LmE)을 추출하여 HL-60 세포에 처리한 다음 세포증식 억제 효과를 보고자 하였다. 세포 생존율 및 세포고사를 확인하여 세포를 죽음으로 유도하는 지 파악한 다음 작용기전을 규명하고자 세포주기의 변화 및 ROS 생성을 관찰하였다. 그 결과, LmSup와 LmE가 급성 전골수구성 백혈병(APL) 세포인 HL-60의 세포고사를 유도하고, sub G0/G1기 증가로 세포주기를 비정상적으로 차단함으로써 세포고사를 유도함을 확인하였다. 이때, ROS가 관여함을 관찰하였다. 이를 통해, LmSup 또는 LmE의 구체적인 항암효과 및 기전 분석을 통해 난치병인 APL의 치료 방법 및 치료제 개발에 기여하고자 한다.

Keywords

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