Acetyl-macrocalin B suppresses tumor growth in esophageal squamous cell carcinoma and exhibits synergistic anti-cancer effects with the Chk1/2 inhibitor AZD7762
Wang, Jing-Nan1,2; Che, Yun1,2; Yuan, Zu-Yang1,2; Lu, Zhi-Liang1,2; Li, Yuan1,2; Zhang, Zhi-Rong1,2; Li, Ning1,2; Li, Ren-Da1,2; Wan, Jun3; Sun, Han-Dong3; Sun, Nan1,2; Puno, Pema-Tenzin3; He, Jie1,2
2019-02-15
Source PublicationTOXICOLOGY AND APPLIED PHARMACOLOGY
ISSN0041-008X
Volume365Pages:71-83
AbstractNatural products derived from herbal medicines have become a major focus of anti-cancer drug discovery studies. Acetyl-macrocalin B (A-macB) is an ent-diterpenoid isolated from Isodon silvatica. This study aimed to examine the effect and molecular action of A-macB in esophageal squamous cell carcinoma (ESCC) and explore possible drug synergistic modalities. A-macB induced cellular reactive oxygen species (ROS) generation, initiated the p38 mitogen-activated protein kinase (MAPK) signaling pathway, and triggered the caspase-9-dependent apoptosis cascade in ESCC cells. The ROS scavenger N-acetylcysteine (NAC) and the specific p38 inhibitor 5B203580 reversed the effects of A-macB on the p38 network and thus rescued ESCC cells from apoptosis. The cellular ROS increase was at least partially due to the suppression of glutathione-S-transferase P1 (GSTP1) by A-macB. A-macB also upregulated the Chk1/Chk2-Cdc25C/Cdc2/Cyclin B1 axis to induce G2/M phase arrest. The cell growth inhibition induced by A-macB was further enhanced by AZD7762, a specific Chk1/Chk2 inhibitor, with a combination index (CI) of < 1. Moreover, A-macB efficiently suppressed xenograft growth without inducing significant toxicity, and AZD7762 potentiated the effects of A-macB in the suppression of tumor growth in vivo. Taken together, A-macB is a promising lead compound for ESCC and exerts synergistic anti-cancer effects with AZD7762.
KeywordAcetyl-macrocalin B Reactive oxygen species p38 MAPK Chk1/Chk2 Esophageal squamous cell carcinoma
Indexed BySCI
Language英语
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/64178
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorSun, Nan; Puno, Pema-Tenzin; He, Jie
Affiliation1.Chinese Acad Med Sci, Canc Hosp, Natl Clin Res Ctr Canc, Natl Canc Ctr,Dept Thorac Surg, 17 Panjiayuan Nan Li, Beijing 100021, Peoples R China
2.Peking Union Med Coll, 17 Panjiayuan Nan Li, Beijing 100021, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
Recommended Citation
GB/T 7714
Wang, Jing-Nan,Che, Yun,Yuan, Zu-Yang,et al. Acetyl-macrocalin B suppresses tumor growth in esophageal squamous cell carcinoma and exhibits synergistic anti-cancer effects with the Chk1/2 inhibitor AZD7762[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2019,365:71-83.
APA Wang, Jing-Nan.,Che, Yun.,Yuan, Zu-Yang.,Lu, Zhi-Liang.,Li, Yuan.,...&He, Jie.(2019).Acetyl-macrocalin B suppresses tumor growth in esophageal squamous cell carcinoma and exhibits synergistic anti-cancer effects with the Chk1/2 inhibitor AZD7762.TOXICOLOGY AND APPLIED PHARMACOLOGY,365,71-83.
MLA Wang, Jing-Nan,et al."Acetyl-macrocalin B suppresses tumor growth in esophageal squamous cell carcinoma and exhibits synergistic anti-cancer effects with the Chk1/2 inhibitor AZD7762".TOXICOLOGY AND APPLIED PHARMACOLOGY 365(2019):71-83.
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