Acetyl-macrocalin B, an ent-kaurane diterpenoid, initiates apoptosis through the ROS-p38-caspase 9-dependent pathway and induces G2/M phase arrest via the Chk1/2-Cdc25C-Cdc2/cyclin B axis in non-small cell lung cancer
Wang, Jing-Nan1,2; Zhang, Zhi-Rong1,2; Che, Yun1,2; Yuan, Zu-Yang1,2; Lu, Zhi-Liang1,2; Li, Yuan1,2; Li, Ning1,2; Wan, Jun3; Sun, Han-Dong3; Sun, Nan1,2; Puno, Pema-Tenzin3; He, Jie1,2
2018
发表期刊CANCER BIOLOGY & THERAPY
ISSN1538-4047
卷号19期号:7页码:609-621
摘要Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and novel effective drugs against NSCLC are urgently needed. Isodon species are rich in ent-kaurane diterpenoids that have been reported to have antitumor bioactivity. Acetyl-macrocalin B (A-macB) is a novel ent-kaurane diterpenoid isolated from Isodon silvatica, and its antitumor efficacy against NSCLC and the underlying mechanisms were scrutinized in depth. The viability of cells treated with A-macB was detected by CCK-8 and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. The mechanisms were investigated by detecting ROS and performing western blotting and verification experiments with specific inhibitors. The in vivo effect of A-macB was explored in a nude mouse xenograft model. A-macB effectively inhibited H1299 and A549 cell viability, triggered apoptosis and delayed cells in the G2/M phase. A-macB induced cellular ROS production and then activated the p38 MAPK-mediated, caspase 9-dependent apoptotic pathway. Both the ROS scavenger NAC and the specific p38 inhibitor SB203580 inactivated the function of p38 induced by A-macB, thus preventing cells from apoptosis. A-macB activated the Chk1/2-Cdc25C-Cdc2/cyclin B1 axis to induce G2/M phase arrest. AZD7762 abrogated the function of Chk1/2, abolished the G2/M delay and enhanced the cytotoxicity of A-macB. Moreover, A-macB efficiently suppressed tumor growth in a mouse xenograft model without noticeable toxicity to normal tissues. Having both efficacy and relative safety, A-macB is a potential lead compound that is worthy of further exploration for development as an anticancer agent.
关键词Acetyl-macrocalin b Reactive Oxygen Species P38 Mapk Apoptosis Chk1 Chk2 G2 m Phase Arrest Nsclc
DOI10.1080/15384047.2018.1449613
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/61358
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Acad Med Sci, Canc Hosp, Dept Thorac Surg, Natl Canc Ctr, Beijing, Peoples R China
2.Peking Union Med Coll, Beijing, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China
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Wang, Jing-Nan,Zhang, Zhi-Rong,Che, Yun,et al. Acetyl-macrocalin B, an ent-kaurane diterpenoid, initiates apoptosis through the ROS-p38-caspase 9-dependent pathway and induces G2/M phase arrest via the Chk1/2-Cdc25C-Cdc2/cyclin B axis in non-small cell lung cancer[J]. CANCER BIOLOGY & THERAPY,2018,19(7):609-621.
APA Wang, Jing-Nan.,Zhang, Zhi-Rong.,Che, Yun.,Yuan, Zu-Yang.,Lu, Zhi-Liang.,...&He, Jie.(2018).Acetyl-macrocalin B, an ent-kaurane diterpenoid, initiates apoptosis through the ROS-p38-caspase 9-dependent pathway and induces G2/M phase arrest via the Chk1/2-Cdc25C-Cdc2/cyclin B axis in non-small cell lung cancer.CANCER BIOLOGY & THERAPY,19(7),609-621.
MLA Wang, Jing-Nan,et al."Acetyl-macrocalin B, an ent-kaurane diterpenoid, initiates apoptosis through the ROS-p38-caspase 9-dependent pathway and induces G2/M phase arrest via the Chk1/2-Cdc25C-Cdc2/cyclin B axis in non-small cell lung cancer".CANCER BIOLOGY & THERAPY 19.7(2018):609-621.
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