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Cryptotanshinone induces pro-death autophagy through JNK signaling mediated by reactive oxygen species generation in lung cancer cells
Hao W.1; Zhang X.1; Zhao W.1; Zhu H.2; Liu Z.-Y.3,4; Lu J.1; Chen X.1
2016
Source PublicationAnti-Cancer Agents in Medicinal Chemistry
ISSN18715206
Volume16Issue:5Pages:593
Abstract

Cryptotanshinone (CTS), a natural product isolated from Salvia miltiorrhiza Bunge, demonstrates anticancer effect. Previous reports showed that CTS induced caspase-independent cell death. Here, we reported that CTS induced pro-death autophagy in human lung cancer cells. CTS inhibited the proliferation of A549 cells in a time- and concentration- dependent manner. CTS triggered autophagy as confirmed by monodansylcadaverine staining, transmission electron microscopy analysis, as well as western blot detection of microtubule-associated protein light-chain 3 (LC3). CTS induced intracellular reactive oxygen species (ROS) formation in a concentration- and time-dependent manner, which was reversed by N-acetyl-L-cysteine (NAC), catalase, diphenyleneiodonium (DPI), pyrrolinodimethylthiocarbamate (PDTC), and dicumarol. Furthermore, CTS-induced autophagy was inhibited by NAC, JNK siRNA and SP600125. NAC reversed CTS-induced JNK phosphorylation. NAC, 3-methyladenine (3-MA), and SP600125 partly reversed CTS-induced cell death. In addition, CTS (10 mg/kg) dramatically inhibited tumor growth by 48.3% in A549 xenograft nude mice, which was completely reversed by NAC (50 mg/kg) co-treatment. Our findings showed that CTS induced pro-death autophagy through activating JNK signaling mediated by increasing intracellular ROS production. © 2016 Bentham Science Publishers.

KeywordAutophagy Cancer Cryptotanshinone Jnk Reactive Oxygen Species
DOI10.2174/1871520615666150907093036
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology ; Pharmacology & Pharmacy
WOS SubjectOncology ; Chemistry, Medicinal
WOS IDWOS:000373800300006
The Source to ArticleScopus
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Cited Times [WOS]:13   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
2.Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310003, Zhejiang, Peoples R China
3.Chinese Acad Med Sci, Inst Canc, Beijing 100730, Peoples R China
4.Peking Union Med Coll, Beijing 100021, Peoples R China
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Hao W.,Zhang X.,Zhao W.,et al. Cryptotanshinone induces pro-death autophagy through JNK signaling mediated by reactive oxygen species generation in lung cancer cells[J]. Anti-Cancer Agents in Medicinal Chemistry,2016,16(5):593.
APA Hao W..,Zhang X..,Zhao W..,Zhu H..,Liu Z.-Y..,...&Chen X..(2016).Cryptotanshinone induces pro-death autophagy through JNK signaling mediated by reactive oxygen species generation in lung cancer cells.Anti-Cancer Agents in Medicinal Chemistry,16(5),593.
MLA Hao W.,et al."Cryptotanshinone induces pro-death autophagy through JNK signaling mediated by reactive oxygen species generation in lung cancer cells".Anti-Cancer Agents in Medicinal Chemistry 16.5(2016):593.
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