The quinone-based derivative, HMNQ induces apoptotic and autophagic cell death by modulating reactive oxygen species in cancer cells
- 주제(키워드) Anticancer drug , Apoptosis , Autophagy , Natural compound , Reactive oxygen species (ROS)
- 등재 SCIE, SCOPUS
- 발행기관 Impact Journals LLC
- 발행년도 2017
- URI http://www.dcollection.net/handler/ewha/000000155899
- 본문언어 영어
- Published As http://dx.doi.org/10.18632/oncotarget.21005
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
8-Hydroxy-2-methoxy-1,4-naphthoquinone (HMNQ), a natural compound isolated from the bark of Juglans sinensis Dode, displays cytotoxic activity against various human cancer cells. However, the molecular mechanism of the anticancer effect is unclear. In this study, we examined the cytotoxic mechanism of HMNQ at the molecular level in human cancer cells. Cells were treated with HMNQ in a dose- or time-dependent manner. HMNQ treatment inhibited cell viability, colony formation and cell migration, indicating that HMNQ induced cancer cell death. HMNQ-treated cells resulted in apoptotic cell death through PARP-1 cleavage, Bax upregulation and Bcl-2 downregulation. HMNQ was also observed to induce autophagy by upregulating Beclin-1 and LC3. Furthermore, HMNQ induced reactive oxygen species (ROS) production, which was attenuated by the ROS scavengers, NAC and GSH. Finally, HMNQ increased expression of JNK phosphorylation and the JNK inhibitor SP600125 rescued HMNQinduced cell death, suggesting that the cytotoxicity of HMNQ is mediated by the JNK signaling pathway. Taken together, our findings show that HMNQ exhibits anticancer activity through induction of ROS-mediated apoptosis and autophagy in human cancer cells. These data suggest the potential value of HMNQ as a natural anticancer drug. © Lee et al.
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