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Apoptotic Cell Death of Human Lung Carcinoma A549 Cells by an Aqueous Extract from the Roots of Platycodon grandiflorum

길경 수용액 추출물에 의한 인체 폐암세포의 apoptosis 유발에 관한 연구

  • 이성열 (동의대학교 한의과대학 내과학교실) ;
  • 이재훈 (동의대학교 한의과대학 생화학교실 및 한의학연구소) ;
  • 김원일 (동의대학교 한의과대학 내과학교실) ;
  • 배송자 (신라대학교 자연과학대학 식품영양학과) ;
  • 박동일 (동의대학교 한의과대학 내과학교실) ;
  • 최영현 (동의대학교 한의과대학 생화학교실 및 한의학연구소)
  • Published : 2003.04.01

Abstract

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P grandiflorum have been reported to have wide ranging health benefits. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the growth of human lung carcinoma A549 cells. Upon treatment with AEPG, a concentration-dependent inhibition of cell growth was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that AEPG increased populations of apoptotic-sub Gl phase. Immunoblot and quantitative RT-PCR analyses indicated that the expressions of Bcl-2 was down-regulated but Bax was up-regulated in AEPG-treated A549 cells. The expression of active form of caspase-3 by AEPG treatment was markedly increased, and the levels of poly(ADP-ribose) polymerase (PARP) and $\beta$-catenin, its target proteins, were decreased in a concentration dependent manner. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

전통 한의학에서 많이 사용되는 길경(Platycodi radix)은 도라지(Platycodon grandiflorum A. DC)의 뿌리 껍질을 벗기거나 또는 그대로 말린 것을 말하며, 염증성 호흡기 질환에 많이 사용되어져 오고 있다. 본 연구에서는 길경 수용액 추출물의 항암 활성 기전해석의 일환으로 A549 인체 폐암세포의 성장에 미치는 영향을 조사하였다. 길경 추출물의 처리에 의하여 처리 농도 의존적으로 암세포의 성장이 억제되었으며, 이는 apoptosis의 유발과 관련이 있었다. 즉 염색체 응축에 의한 apoptotic body의 출현과 sub-Gl기에 속하는 세포의 빈도가 길경 추출물 처리에 의하여 농도 의존적으로 증가하였다. Immunoblot 및 RT-PCR분석에서 길경 추출물의 처리에 의하여 Bcl-2의 mRNA 및 단백질의 발현은 감소되었으며, Bax의 발현이 증가됨을 알 수 있었다. 또한 길경 추출물의 처리에 의하여 caspase-3가 활성화되었으며, 이에 따른 PARP 및 $\beta$-catenin의 단백질 발현 감소 현상을 관찰할 수 있었다. 이러한 결과들은 길경 추출물을 이용한 인체 암세포의 성장억제제의 개발 가능성이 있음을 시사하여 준다.

Keywords

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