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Correction published on 21 April 2020, see Int. J. Mol. Sci. 2020, 21(8), 2915.
Article

(+)-Usnic Acid Induces ROS-dependent Apoptosis via Inhibition of Mitochondria Respiratory Chain Complexes and Nrf2 Expression in Lung Squamous Cell Carcinoma

by 1,2,3,4, 1,2,3,4, 1,2,3,4, 1,2,3,4, 1 and 1,2,3,4,*
1
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
2
Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou 510006, China
3
Key Laboratory of New Drug Discovery and Evaluation of ordinary universities of Guangdong province, Guangdong Pharmaceutical University, Guangzhou 510006, China
4
Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 876; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030876
Received: 1 January 2020 / Revised: 24 January 2020 / Accepted: 27 January 2020 / Published: 29 January 2020
(This article belongs to the Section Molecular Oncology)
Lung squamous cell carcinoma (LUSC) has a poor prognosis, in part due to poor therapeutic response and limited therapeutic alternatives. Lichens are symbiotic organisms, producing a variety of substances with multiple biological activities. (+)-Usnic acid, an important biologically active metabolite of lichens, has been shown to have high anti-cancer activity at low doses. However, there have been no reports regarding the effect of (+)-usnic acid on LUSC cells. This study found that (+)-usnic acid reduced viability and induced apoptosis in LUSC cells by reactive oxygen species (ROS) accumulation. (+)-Usnic acid induced mitochondria-derived ROS production via inhibition of complex I and complex III of the mitochondrial respiratory chain (MRC). Interestingly, the elimination of mitochondrial ROS by Mito-TEMPOL only partially reversed the effect of (+)-usnic acid on cellular ROS production. Further study showed that (+)-usnic acid also induced ROS production via reducing Nrf2 stability through disruption of the PI3K/Akt pathway. The in vitro and in vivo xenograft studies showed that combined treatment of (+)-usnic acid and paclitaxel synergistically suppressed LUSC cells. In conclusion, this study indicates that (+)-usnic acid induces apoptosis of LUSC cells through ROS accumulation, probably via disrupting the mitochondrial respiratory chain (MRC) and the PI3K/Akt/Nrf2 pathway. Therefore, although clinical use of (+)-usnic acid will be limited due to toxicity issues, derivatives thereof may turn out as promising anticancer candidates for adjuvant treatment of LUSC. View Full-Text
Keywords: (+)-usnic acid; lung squamous cell carcinoma; reactive oxygen species (ROS); paclitaxel (+)-usnic acid; lung squamous cell carcinoma; reactive oxygen species (ROS); paclitaxel
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MDPI and ACS Style

Qi, W.; Lu, C.; Huang, H.; Zhang, W.; Song, S.; Liu, B. (+)-Usnic Acid Induces ROS-dependent Apoptosis via Inhibition of Mitochondria Respiratory Chain Complexes and Nrf2 Expression in Lung Squamous Cell Carcinoma. Int. J. Mol. Sci. 2020, 21, 876. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030876

AMA Style

Qi W, Lu C, Huang H, Zhang W, Song S, Liu B. (+)-Usnic Acid Induces ROS-dependent Apoptosis via Inhibition of Mitochondria Respiratory Chain Complexes and Nrf2 Expression in Lung Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2020; 21(3):876. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030876

Chicago/Turabian Style

Qi, Wanchen, Changpeng Lu, Huiliang Huang, Weinan Zhang, Shaofei Song, and Bing Liu. 2020. "(+)-Usnic Acid Induces ROS-dependent Apoptosis via Inhibition of Mitochondria Respiratory Chain Complexes and Nrf2 Expression in Lung Squamous Cell Carcinoma" International Journal of Molecular Sciences 21, no. 3: 876. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030876

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