Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Anticancer activity of chloroform extract of Citrus unshiu Markovich peel against glioblastoma stem cells

교모세포종 암줄기세포에 대한 진피 소수성 추출물의 항암 활성

  • Kim, Yu Jin (Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University) ;
  • Sim, Ye Eun (Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University) ;
  • Jung, Hye Jin (Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University)
  • 김유진 (선문대학교 제약생명공학과) ;
  • 심예은 (선문대학교 제약생명공학과) ;
  • 정혜진 (선문대학교 제약생명공학과)
  • Received : 2021.10.15
  • Accepted : 2021.11.29
  • Published : 2022.02.28
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Abstract

Glioblastoma is the most common primary malignant brain tumor and has an extremely poor prognosis. Glioblastoma stem cells (GSCs) contribute to tumor initiation, recurrence, and resistance to therapy, and are thus a key therapeutic target. The peel of Citrus unshiu Markovich has been used in traditional medicine in East Asia to treat various diseases. In this study, we investigated the anticancer activity and molecular mechanism of the chloroform extract of this natural product (CECU) in U87MG GSCs. The results show that CECU inhibited the proliferation, tumorsphere formation, and migration of U87MG GSCs by causing cell cycle arrest at the G0/G1 phase and apoptosis. In addition, CECU downregulated key cancer stemness regulators, including CD133, Oct4, Nanog, integrin α6, ALDH1A1, and STAT3 signaling in U87MG GSCs. Furthermore, CECU significantly suppressed in vivo tumor growth of U87MG GSCs in a chorioallantoic membrane model. Therefore, CECU can be utilized as a natural medicine for the prevention and treatment of glioblastoma.

본 연구에서는 진피 소수성 추출물(CECU)의 U87MG 교모세포종 암줄기세포에 대한 항암 활성을 확인하였다. 그 결과, CECU는 25-200 ㎍/mL의 농도 범위에서 U87MG 교모세포종 암줄기세포의 증식, 종양구체 형성과 이동능력을 유의적으로 저해하였다. 특히, CECU는 G0/G1기에서 세포주기 정지와 세포사멸을 유도하여 교모세포종 암줄기세포의 증식을 억제할 수 있었다. 게다가, 교모세포종 암줄기세포에 대한 CECU의 항암 활성은 CD133, Oct4, Nanog, Integrin α6, ALDH1A1과 같은 줄기세포능 조절인자들의 발현과 STAT3 신호전달경로를 저해함으로써 유도된 것임을 확인하였다. 마지막으로, CAM assay를 통해 CECU가 U87MG 교모세포종 암줄기세포의 in vivo 종양 형성을 효과적으로 억제함을 입증하였다. 따라서, 본 연구는 진피 소수성 추출물이 주요 stemness marker들의 발현과 핵심 stemness 조절 신호전달경로를 억제함으로써 U87MG 교모세포종 암줄기세포에 대한 항암 활성을 나타냄을 입증하여, 교모세포종의 예방 및 치료를 위한 천연물 소재로서의 활용 가능성을 새롭게 제시하였다.

Keywords

Acknowledgement

본 논문은 한국연구재단 기초연구사업(NRF-2019R1A2C1009033, NRF-2021R1I1A3050093)의 지원에 의해 이루어진 것임.

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