HepG2 인체 간암세포의 ROS 생성 및 ERK/Akt 신호전달 경로 조절을 통한 sanguinarine의 apoptosis 유도

Hwang, Ju Yeong;Cho, Yung Hyun

  • 투고 : 2015.07.13
  • 심사 : 2015.09.07
  • 발행 : 2015.09.30


혈근초(Sanguinaria canadensis)에서 처음 분리된 sanguinarine은 항산화, 항암 및 면역 증강 등의 효능이 있는 것으로 알려진 alkaloid 계열 물질 중의 하나이다. 본 연구에서는 인체간암 HepG2 세포를 대상으로 sanguinarine의 apoptosis 유도 효능 및 관련 기전 해석을 시도하였다. 본 연구의 결과에 의하면 sanguinarine은 HepG2 간암세포의 증식을 처리 농도 의존적으로 억제하였으며, 이는 apoptosis 유도와 연관성이 있었다. Sanguinarine에 의한 apoptosis 유도에는 Fas 및 Bax의 발현 증가, 미토콘드리아에서 세포질로의 cytochrome c 유리 및 MMPl (Δψm)의 소실을 동반하였다. Sanguinarine은 intrinsic 및 extrinsic apoptosis pathway의 활성에 관여하는 initiator caspase인 caspase-9와 -8의 활성과 effector caspase인 caspase-3의 활성 및 PARP 단백질의 단편화를 유발하였다. Sanguinarine은 또한 ROS의 생성을 촉진시켰으며, N-acetylcysteine 처리에 의한 ROS의 생성을 차단하였을 경우, sanguinarine에 의한 apoptosis 효능이 완벽하게 차단되었다. 아울러 sanguinarine은 Akt의 인산화를 억제한 반면, MAPKs의 인산화를 촉진시켰으며, 특히 PI3K와 ERK의 선택적 억제제는 sanguinarine에 의한 HepG2 간암세포의 증식을 더욱 억제시켰다. 따라서 sanguinarine에 의한 HepG2 간암세포의 apoptosis 유발에는 ROS 생성 의존적인 intrinsic 및 extrinsic signaling pathway가 동시에 활성화되며, PI3K/Akt 및 ERK 신호계가 관여함을 알 수 있었다.


Apoptosis;extracellular signal-regulated kinase (ERK);PI3K/Akt;reactive oxygen species (ROS);sanguinarine


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피인용 문헌

  1. Extract from Artemisia annua Linn? Induces Apoptosis through the Mitochondrial Signaling Pathway in HepG2 Cells vol.45, pp.12, 2016,