Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Polyamine Induces Apoptosis Through the Calcium Signaling in Human Prostate Cancer Cells

전립선암세포에 있어서 폴리아민에 의한 칼슘신호와 세포사멸

  • Song Hwi-June (Department of Biology, Pusan National University) ;
  • Kim Ji-Young (Department of Biology, Pusan National University) ;
  • Yoo Mi-Ae (Institute of Genetic Engineering, Pusan National University) ;
  • Chung Hae-Young (Institute of Genetic Engineering, Pusan National University) ;
  • Kim Jong-Min (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Kim Byeong-Gee (Department of Biology, Pusan National University)
  • 송휘준 (부산대학교 생물학과) ;
  • 김지영 (부산대학교 생물학과) ;
  • 유미애 (부산대학교 유전공학연구소) ;
  • 정해영 (부산대학교 유전공학연구소) ;
  • 김종민 (동아대학교 의과대학 해부학교실) ;
  • 김병기 (부산대학교 생물학과)
  • Published : 2006.06.01
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Abstract

Polyamines are essential for the normal cell growth and differentiation. They are also known to have paradoxical dual effects on cell proliferation. In this paper we show that the excess amount of polyamines induces apoptosis through the modulation of calcium signaling in LNCaP human prostate cancer cells. Polyamines, particularly spermidine and spermine, stimulated cell proliferation at a lower concentration (under 10 ${\mu}M$), but it inhibited cell viability at a higher concentration (40 ${\mu}M$). The levels of intracellular $Ca^{2+}$ concentration were increased only at a high concentration of polyamines treatment without any noticeable changes at lower concentrations. Nifedipine did not alter the increase of polyamine-induced $Ca^{2+}$ levels, but flufenamic acid totally abolished the increase of intracellular $Ca^{2+}$ levels. These results mean that polyamines induce $Ca^{2+}$ influx from the surroundings through nonselective cation channels on the cell membrane. The expression of Bcl-2 protein was almost completely blocked, but the level of Bax protein was increased dramatically in the cells treated with high concentration of polyamine. The present study shows that polyamines at a high concentration induce apoptosis through the modulation of intracellular calcium signaling. The increase of intracellular calcium level induced by polyamines, was possibly a result from the extracellular calcium influx through the nonselective cation channels.

폴리아민은 거의 모든 세포에 있어서 성장과 분화에 필수적인 물질이다. 이들 폴리아민의 기작은 상당히 복잡하고 다양하여 그 정확한 작용기전은 아직 확실하지가 않다. 본 논문에서는 폴리아민이 세포 증식을 유도 하기도 하지만 일정농도 이상에서는 오히려 세포사멸을 초래한다는 결과를 밝히고자 한다. 본 실험에 사용된 인간의 전립선 암세포(LNCaP cells)에 있어서, 폴리아민 가운데 putrescien은 세포 증식에 거의 영향을 미치지 않았으나 spermidine과 spermine의 경우 10 ${\mu}M$ 이하에서는 세포 증식을 촉진하였다. 그러나, 20 ${\mu}M$ 이상의 농도에서는 농도와 시간의존적으로 세포사별을 유도 하였다. 폴리아민 처리에 의한 세포사멸의 초기과정인 핵 응축과 염색질 condensation이 Hoechst와 PI 염색에서 뚜렷이 관찰되었다. 또한, 폴리아민 처리시 anti-apoptotic protein으로 알려진 Bcl-2 protein의 발현은 거의 완전히 억제된 반면, pro-apoptotic protein으로 알려진 Bax의 발현은 현저히 증대되었다. 본 연구의 결과에 따르면, 폴리아민에 의해서 유도되는 세포사멸은 세포 내 칼슘농도 변화에 의한 것으로 사료된다. 전립선 암세포에 있어서 폴리아민 처리시 시간과 농도 의존적으로 세포 내 칼슘농도가 증가되었다. 세포막을 통한 칼슘이동을 억제하는 nifedipine과 flufenamic acid 등의 억제제를 처리한 실험 결과 세포내 칼슘증가는 세포 내부의 저장소로부터 칼슘의 유출보다는 주로 세포막상에 있는 비선택적 칼슘통로를 통한 외부의 칼슘 유입에 의한 것으로 판단된다.

Keywords

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