Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo
Identifieur interne : 000199 ( an2020/Analysis ); précédent : 000198; suivant : 000200Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo
Auteurs : Jiangjiang Fan [République populaire de Chine] ; Dongmei Ren [République populaire de Chine] ; Jinxia Wang [République populaire de Chine] ; Xiaoqing Liu [République populaire de Chine] ; Huaran Zhang [République populaire de Chine] ; Mingsheng Wu [République populaire de Chine] ; Guotao Yang [République populaire de Chine]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2020.
Abstract
Worldwide, lung cancer remains a leading cause of cancer mortality. Bruceine D (BD) has been shown to induce pancreatic cancer cell death via several different mechanisms. In this study, we demonstrated that BD inhibited lung cancer cell proliferation. Apoptosis and autophagy were the most important mechanisms involved in BD-induced lung cancer cell death, and complete autophagic flux was observed in A549 and NCI-H292 cells. In addition, BD significantly improved intracellular reactive oxygen species (ROS) levels. BD-mediated cell apoptosis and autophagy were almost inhibited in cells pretreated with N-acetylcysteine (NAC), an ROS scavenger. Furthermore, MAPK signaling pathway activation contributed to BD-induced cell proliferation inhibition and NAC could eliminate p-ERK and p-JNK upregulation. Finally, an in vivo study indicated that BD inhibited the growth of lung cancer xenografts. Overall, BD is a promising candidate for the treatment of lung cancer owing to its multiple mechanisms and low toxicity.
Url:
DOI: 10.1038/s41419-020-2317-3
PubMed: 32071301
PubMed Central: 7028916
Affiliations:
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PMC:7028916Le document en format XML
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<front><div type="abstract" xml:lang="en"><p id="Par1">Worldwide, lung cancer remains a leading cause of cancer mortality. Bruceine D (BD) has been shown to induce pancreatic cancer cell death via several different mechanisms. In this study, we demonstrated that BD inhibited lung cancer cell proliferation. Apoptosis and autophagy were the most important mechanisms involved in BD-induced lung cancer cell death, and complete autophagic flux was observed in A549 and NCI-H292 cells. In addition, BD significantly improved intracellular reactive oxygen species (ROS) levels. BD-mediated cell apoptosis and autophagy were almost inhibited in cells pretreated with N-acetylcysteine (NAC), an ROS scavenger. Furthermore, MAPK signaling pathway activation contributed to BD-induced cell proliferation inhibition and NAC could eliminate p-ERK and p-JNK upregulation. Finally, an in vivo study indicated that BD inhibited the growth of lung cancer xenografts. Overall, BD is a promising candidate for the treatment of lung cancer owing to its multiple mechanisms and low toxicity.</p>
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<author><name sortKey="Klionsky, Dj" uniqKey="Klionsky D">DJ Klionsky</name>
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<author><name sortKey="Itakura, E" uniqKey="Itakura E">E Itakura</name>
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<biblStruct><analytic><author><name sortKey="Yan, X" uniqKey="Yan X">X Yan</name>
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<biblStruct><analytic><author><name sortKey="Scherz Shouval, R" uniqKey="Scherz Shouval R">R Scherz-Shouval</name>
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<author><name sortKey="Elazar, Z" uniqKey="Elazar Z">Z Elazar</name>
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</biblStruct>
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<author><name sortKey="Fan, D" uniqKey="Fan D">D Fan</name>
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<biblStruct><analytic><author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name>
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<biblStruct><analytic><author><name sortKey="Wang, Lj" uniqKey="Wang L">LJ Wang</name>
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<affiliations><list><country><li>République populaire de Chine</li>
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<tree><country name="République populaire de Chine"><noRegion><name sortKey="Fan, Jiangjiang" sort="Fan, Jiangjiang" uniqKey="Fan J" first="Jiangjiang" last="Fan">Jiangjiang Fan</name>
</noRegion>
<name sortKey="Liu, Xiaoqing" sort="Liu, Xiaoqing" uniqKey="Liu X" first="Xiaoqing" last="Liu">Xiaoqing Liu</name>
<name sortKey="Ren, Dongmei" sort="Ren, Dongmei" uniqKey="Ren D" first="Dongmei" last="Ren">Dongmei Ren</name>
<name sortKey="Wang, Jinxia" sort="Wang, Jinxia" uniqKey="Wang J" first="Jinxia" last="Wang">Jinxia Wang</name>
<name sortKey="Wu, Mingsheng" sort="Wu, Mingsheng" uniqKey="Wu M" first="Mingsheng" last="Wu">Mingsheng Wu</name>
<name sortKey="Yang, Guotao" sort="Yang, Guotao" uniqKey="Yang G" first="Guotao" last="Yang">Guotao Yang</name>
<name sortKey="Zhang, Huaran" sort="Zhang, Huaran" uniqKey="Zhang H" first="Huaran" last="Zhang">Huaran Zhang</name>
</country>
</tree>
</affiliations>
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