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Dehydrocostus Lactone Induces Apoptosis and Cell Cycle Arrest through Regulation of JAK2/STAT3/PLK1 Signaling Pathway in Human Esophageal Squamous Cell Carcinoma Cells
- Source :
- Anti-Cancer Agents in Medicinal Chemistry. 22:1742-1752
- Publication Year :
- 2022
- Publisher :
- Bentham Science Publishers Ltd., 2022.
-
Abstract
- Background: Dehydrocostus lactone (DEH), one of the sesquiterpene lactones, has shown extensive pharmaceutical activities, including anti-cancer activity. However, its effects on human esophageal squamous cell carcinoma (ESCC) cells are still unknown. Objective: To investigate the effect of DEH on ESCC cells and the underling molecular mechanisms. Method: The cell proliferation was tested using CCK-8 and colony formation assay. Apoptosis was analyzed by flow cytometry, hoechst staining and caspase-3 activity assay. Cell cycle was analyzed by flow cytometry. IL-6 (STAT3 activator) was used to activate JAK2/STAT3 pathway. Immunofluorescence assay was performed to detect intracellular location of STAT3. SiRNA transfection was performed to knock down the expression of PLK1. The protein expression was analyzed by western blotting assay. Result: DHE treatment significantly reduced the viability of ESCC cells through apoptosis induction and cell cycle arrest. Furthermore, DHE treatment significantly inhibited the phosphorylation of JAK2 and STAT3. IF assay showed that the distribution of STAT3 in the nucleus was decreased by DHE treatment. In addition, coculture with IL-6 significantly prevented the inhibition of phosphorylation of JAK2 and STAT3 by DHE treatment and partly reversed the effect of DHE on ESCC cells. Moreover, DHE treatment significantly down-regulated the expression of PLK1, which was partly reversed by IL-6 coculture. Finally, knock down of PLK1 using siRNA reduced the viability of ESCC cells and induced apoptosis and cell cycle arrest Conclusion: Our study demonstrated that DHE has a potent anti-cancer effect on ESCC cells through apoptosis induction and cell cycle arrest via JAK2/STAT3/PLK signaling pathway.
- Subjects :
- STAT3 Transcription Factor
Cancer Research
Cell cycle checkpoint
Esophageal Neoplasms
Apoptosis
Flow cytometry
Lactones
Cell Line, Tumor
medicine
Humans
RNA, Small Interfering
Cell Proliferation
Pharmacology
medicine.diagnostic_test
Interleukin-6
Chemistry
Cell growth
Cell Cycle Checkpoints
Transfection
Janus Kinase 2
Cell cycle
Cancer research
Molecular Medicine
Esophageal Squamous Cell Carcinoma
Signal transduction
Sesquiterpenes
Intracellular
Signal Transduction
Subjects
Details
- ISSN :
- 18715206
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Anti-Cancer Agents in Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....2fed3476be94ae84c52dc24ec9aeacf2