Discovery of Sesquiterpene Lactones with Cytotoxicity from the Herb of Youngia japonica

Author:

Ye Xian‐Sheng1,Lin Kuan1,Tao Xiao‐Qing1,Shang Jin‐Ting1,Gui Yu‐Ran1,Zhu Shu‐Xiu2,Zhou Le3,Xia Yi‐Yuan1,Liu Wei1,Sun Bin‐Lian1,Chen Hai‐Feng4,Shu Xi‐Ji1

Affiliation:

1. Hubei Key Laboratory of Cognitive and Affective Disorders Institute of Biomedical Sciences, School of Medicine Jianghan University Wuhan 430056 China

2. Department of Traditional Chinese Medicine School of Medicine Jianghan University Wuhan 430056 China

3. CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia Medica RNAM Center for Marine Microbiology Chinese Academy of Sciences South China Sea Institute of Oceanology Guangzhou 510000 China

4. Fujian Provincial Key Laboratory of Innovative Drug Target School of Pharmaceutical Sciences Xiamen University Xiamen 361102 China

Abstract

AbstractIn the process of searching for anti‐breast cancer agents, five sesquiterpene lactones (15), including two previously undescribed ones, yjaponica B‐C (12), were isolated from the herb of Youngia japonica. Their structures were elucidated by spectroscopic data analyses and Marfey's method. Cytotoxic activities of all compounds against A549, U87, and 4T1 cell lines were tested using the CCK8 assay. The result showed that compound 3 possessed the highest cytotoxic activity against 4T1 cells with an IC50 value of 10.60 μM. Furthermore, compound 3 distinctly induced apoptosis, inhibited immigration, and blocked the cell cycle of 4T1 cells. In addition, compound 3 induced the production of reactive oxygen species. Further anticancer mechanism studies showed that compound 3 significantly upregulated expression of the cleaved caspase 3 and PARP, whereas it downregulated the expression of Bcl‐2, cyclin D1, cyclin A2, CDK4, and CDK2. Taken together, our results demonstrate that compound 3 has a high potential of being used as a leading compound for the discovery of new anti‐breast cancer agent.

Funder

Natural Science Foundation of Hubei Province

National Natural Science Foundation of China

Publisher

Wiley

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