Research Papers:

The quinone-based derivative, HMNQ induces apoptotic and autophagic cell death by modulating reactive oxygen species in cancer cells

Eun Byul Lee, Min Gyeong Cheon, Jun Cui, Yoo Jin Lee, Eun Kyoung Seo and Ho Hee Jang _

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Oncotarget. 2017; 8:99637-99648. https://doi.org/10.18632/oncotarget.21005

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Eun Byul Lee1,*, Min Gyeong Cheon1,*, Jun Cui1,2, Yoo Jin Lee3, Eun Kyoung Seo3 and Ho Hee Jang1,4

1Department of Health Sciences and Technology, Graduate School of Medicine, Gachon University, Incheon, South Korea

2Department of Ophthalmology, Affiliated Hospital of Yanbian University, Yanji, Jilin, People’s Republic of China

3College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea

4Department of Biochemistry, College of Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea

*These authors contributed equally to this work

Correspondence to:

Ho Hee Jang, email: [email protected]

Keywords: anticancer drug, natural compound, reactive oxygen species (ROS), apoptosis, autophagy

Received: August 01, 2017     Accepted: August 28, 2017     Published: September 18, 2017


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 HMNQ-induced 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.

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