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Naturally Occurring Sesquiterpene Lactone-Santonin, Exerts Anticancer Effects in Multi-Drug Resistant Breast Cancer Cells by Inducing Mitochondrial Mediated Apoptosis, Caspase Activation, Cell Cycle Arrest, and by Targeting Ras/Raf/MEK/ERK Signaling Pathway

Authors
  • Wu, Zhiqiang1, 2
  • Wang, Chenchen1, 3
  • Huang, Mingzhu1, 3
  • Tao, Zhonghua1, 3
  • Yan, Wangjun1, 2
  • Du, Yiqun1, 3
  • 1 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China
  • 2 Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China
  • 3 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China
Type
Published Article
Journal
Medical Science Monitor
Publisher
"International Scientific Information, Inc."
Publication Date
May 18, 2019
Volume
25
Pages
3676–3682
Identifiers
DOI: 10.12659/MSM.915246
PMID: 31101800
PMCID: PMC6540632
Source
PubMed Central
Keywords
License
Green

Abstract

Background Sesquiterpene lactones have gained tremendous attention owing to their potent anticancer properties. The main focus of this study was to evaluate the anticancer effects of a naturally occurring sesquiterpene lactone, santonin, against human breast cancer SK-BR-3 cells. Material/Methods Cell counting kit 8 assay was used for the determination of cell viability. Apoptosis was detected by DAPI (4′,6-diamidino-2-phenylindole) and annexin V/propidium iodide (IP) staining. Flow cytometry was used for cell cycle analysis and western blotting was used for the estimation of protein expression. Results Results showed that santonin exerts significant anti-proliferative effects on the SK-BR-3 breast cancer cells in a concentration dependent manner. Santonin showed an IC50 of 16 μM against SK-BR-3 cells. DAPI staining showed that santonin caused DNA fragmentation in the SK-BR-3 cells, which is indicative of apoptosis. Annexin V/PI staining showed that apoptotic cell percentage increased up to 34.32% at 32 μM concentration of santonin. Santonin also caused an increase in the expression of Bax, caspase-3, and caspase-9, and a decrease in the expression of Bcl-2. Santonin also caused the arrest of the SK-BR-3 cells at the G2/M phase of the cell cycle and suppressed the expression of cyclin A and B1. Finally, santonin could also block the Raf/MEK/ERK pathway in breast cancer cells. Conclusions The findings of this study suggest the potential for the naturally occurring sesquiterpene lactone santonin in breast cancer treatment and also suggest that it could be developed as a promising anticancer agent.

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