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

Abstract：

: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.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Qi W,Lu C,Huang H,Zhang W,Song S,Liu B

doi

10.3390/ijms21030876

subject

Has Abstract

pub_date

2020-01-29 00:00:00

issue

3

issn

1422-0067

pii

ijms21030876

journal_volume

21

pub_type

杂志文章

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