Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Combined Treatment of Sodium Salicylate and Genistein Induces Incomplete Apoptosis and Necrosis in MCF-7 Multicellular Tumor Spheroids

MCF-7 MTS에서 sodium salicylate과 genistein 복합처리는 불완전한 세포사멸과 세포괴사를 유도한다

  • Lee, Su-Yeon (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Kim, Cho-Hee (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Jeon, Hyun-Min (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Ju, Min-Kyung (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Kim, Min-Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Jeong, Eui-Kyong (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Park, Hye-Gyeong (Nanobiotechnology Center, Pusan National University) ;
  • Kang, Ho-Sung (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
  • 이수연 (부산대학교 자연과학대학 분자생물학과) ;
  • 김초희 (부산대학교 자연과학대학 분자생물학과) ;
  • 전현민 (부산대학교 자연과학대학 분자생물학과) ;
  • 주민경 (부산대학교 자연과학대학 분자생물학과) ;
  • 김민영 (부산대학교 자연과학대학 분자생물학과) ;
  • 정의경 (부산대학교 자연과학대학 분자생물학과) ;
  • 박혜경 (부산대학교 나노바이오테크놀러지 센터) ;
  • 강호성 (부산대학교 자연과학대학 분자생물학과)
  • Received : 2012.07.09
  • Accepted : 2012.09.20
  • Published : 2012.09.30
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Abstract

Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 lung cancer cells, indicating that these two natural chemicals could be used in combination for cancer therapy. In this study, we examined effects of NaSal/genistein combined treatment on other cancer cells and in three-dimensional multicellular tumor spheroid (MTS) and in an in vitro solid tumor model. We found that the combined treatment induces apoptosis in the HCT116 cells and the A549 cells, but not in the MCF-7 cells. Interestingly, the MCF-7 cells responded to the NaSal/genistein combined treatment by undergoing cell death when they were cultivated as MTS. The combined treatment induced apoptosis at an earlier stage in the MCF-7 MTS culture. However, when the MCF-7 MTS was cultivated for a longer period, it induced necrosis rather than apoptosis. We further found that the apoptotic pattern observed in MCF-7 MTS was incomplete: the chromatins were condensed and fragmented, but the nuclear membrane was still intact. Taken together, these results demonstrate that the NaSal/genistein combined treatment induces incomplete apoptosis and necrosis in the MCF-7 MTS culture system.

아스피린과 아스피린의 deacetylated form인 sodium salicylate (NaSal)은 대장암, 폐암 및 유방암을 비롯한 다양한 암의 항암제 활성을 나타내는 것으로 잘 알려져 있다. A549 폐암 세포주에 저농도의 NaSal과 genistein을 함께 복합 처리시 상승작용에 의해 세포사멸을 증가시켜서 NaSal에 의한 암억제 효과를 증대시킴을 이미 밝힌바 있다. 본 연구에서는 A549가 아닌 다른 암세포주와 in vitro solid tumor model인 multicellular spheroids (MTS)을 이용하여 NaSal과 genistein 복합처리 효과를 조사하였다. NaSal/genistein 복합 처리시 A549 세포주와 마찬가지로 HCT116 세포주에서도 세포사멸이 유도되었지만, MCF-7 세포주에서는 유도되지 않았다. 흥미롭게도, MCF-7 세포주는 MTS로 배양되는 동안 NaSal/genistein 복합 처리에 의해 세포 죽음을 나타내었다. 세포 죽음의 형태는 MCF-7 MTS의 발달 단계에 따라 세포사멸 또는 세포괴사로 나타났다. MCF-7 MTS에서의 세포사멸은 불완전한 양상을 보였다. 즉 염색체가 응축되고 쪼개지지만, 핵막은 여전히 관찰되었다. 이상의 연구 결과 NaSal/genistein 복합처리는 MCF-7 MTS 배양 system에서 불완전한 세포사멸과 세포괴사를 일으킴을 알 수 있었다.

Keywords

References

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