Objective: To study the anti-tumor effect and mechanism of parthenolide in gastric cancer cell BGC-823. Methods: The cck8 assay was used to detect the changes of BGC-823 cells viability after treatment with different con-centrations of parthenolide at different time points. The proliferation ability of BGC-823 cells was detected by clone formation assay. And the cell cycle and apoptosis were measured by flow cytometry. Meanwhile, to detect the different in intracellular ROS production levels, the fluorescence assay was used. And with the help of western blotting, cell cycle- and apoptosis-related protein expression can be detected. Results: Parthenolide could inhibit the viability of BGC-823 cells in a dose- and time-dependent manner (P < 0.01). In BGC-823 cells exposed to parthenolide, the apoptosis rate was found significantly increased (P < 0.01), and the protein expression of cleaved-caspase3, cleaved-caspase8, and cleaved-caspase9 significantly increased (P < 0.01); the cell cycle was arrested at G1phase (P < 0.01); the protein levels of CyclinD1 and CyclinE1 decreased (P < 0.01), and the expression of P53 and P21 protein increased (P < 0.01); massive intracellular ROS generation was found (P < 0.01). Furthermore, the nuclear protein levels of c-Myc, E2F1, and NF-κB and the protein level of phosphorylated STAT3 decreased in BGC-823 cells exposed to parthenolide (P < 0.01). Conclusion: Parthenolide may inhibit the proliferation of BGC-823 cells and induce G1-phase cell cycle arrest and apoptosis via inhibiting STAT3-c-Myc-E2F1 axis.
Cite this paper
Zhu, W. , Zhang, H. , Guo, Y. , Ge, K. and Zhou, Y. (2019). Anti-Tumor Effect and Mechanism of Parthenolide in Gastric Cancer Cellline BGC-823. Open Access Library Journal, 6, e5271. doi: http://dx.doi.org/10.4236/oalib.1105271.
Jin, X., Zhou, J., Zhang, Z. and Lv, H. (2018) The Combined Administration of Parthenolide and Ginsenoside CK in Long Circulation Liposomes with Targeted tLyp-1 Ligand Induce Mitochondria-Mediated Lung Cancer Apoptosis. Artificial Cells, Nanomedicine, and Biotechnology, 11, 1-12.
Wang, M.T. and Li, Q.Y. (2015) Parthenolide Could Become a Promising and Stable Drug with Anti-Inflammatory Effects. Natural Product Research, 29, 1092-1101. https://doi.org/10.1080/14786419.2014.981541
Kalia, M., Yadav, V.K., Singh, P.K., et al. (2018) Exploring the Impact of Parthenolide as Anti-Quorum Sensing and Anti-Biofilm Agent against Pseudomonas aeruginosa. Life Sciences, 199, 96-103. https://doi.org/10.1016/j.lfs.2018.03.013
Flores-Lopez, G., Moreno-Lorenzana, D., Ayala-Sanchez, M., et al. (2018) Parthenolide and DMAPT Induce Cell Death in Primitive CML Cells through Reactive Oxygen Species. Journal of Cellular and Molecular Medicine, 22, 4899-4912. https://doi.org/10.1111/jcmm.13755
Duan, D.Z., Zhang, J.M., Yao, J., et al. (2016) Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells. The Journal of Biological Chemistry, 291, 10021-10031. https://doi.org/10.1074/jbc.M115.700591
Wu, C.Q., Chen, F., Rushing, J.W., et al. (2006) Antiproliferative Activities of Parthenolide and Golden Feverfew Extract against Three Human Cancer Cell Lines. Journal of Medicinal Food, 9, 55-61. https://doi.org/10.1089/jmf.2006.9.55
Guo, X.-X., Li, Y., Sun, C., et al. (2014) p53-Dependent Fas Expression Is Critical for Ginsenoside Rh2 Triggered Caspase-8 Activation in HeLa Cells. Protein & Cell, 5, 224-234. https://doi.org/10.1007/s13238-014-0027-2
Choudhary, G.S., Al-Harbi, S. and Almasan, A. (2015) Caspase-3 Activation Is a Critical Determinant of Genotoxic Stress-Induced Apoptosis. Methods in Molecular Biology, 1219, 1-9. https://doi.org/10.1007/978-1-4939-1661-0_1
Talib, W.H. and Al Kury, L.T. (2018) Parthenolide Inhibits Tumor-Promoting Effects of Nicotine in Lung Cancer by Inducing P53-Dependent Apoptosis and Inhibiting VEGF Expression. Biomedicine & Pharmacotherapy, 107, 1488-1495. https://doi.org/10.1016/j.biopha.2018.08.139
Li, C., Ge, Q., Liu, J., et al. (2017) Effects of miR-1236-3p and miR-370-5p on Activation of p21 in Various Tumors and Its Inhibition on the Growth of Lung Cancer Cells. Tumor Biology, 39, 1010428317710824. https://doi.org/10.1177/1010428317710824
Liu, B., Zhou, Z., Zhou, W., et al. (2014) Resveratrol Inhibits Proliferation in Human Colorectal Carcinoma Cells by Inducing G1/S Phase Cell Cycle Arrest and Apoptosis through Caspase/Cyclin-CDK Pathways. Molecular Medicine Reports, 10, 1697-702. https://doi.org/10.3892/mmr.2014.2406
Lee, C.H., Yang, J.R., Chen, C.Y., et al. (2019) Novel STAT3 Inhibitor LDOC1 Targets Phospho-JAK2 for Degradation by Interacting with LNX1 and Regulates the Aggressiveness of Lung Cancer. Cancers (Basel), 11.
Bloom, M.J., Saksena, S.D., Swain, G.P., et al. (2018) The Effects of IKK-Beta Inhibition on Early NF-kappa-B Activation and Transcription of Downstream Genes. Cell Signal, 55, 17-25. https://doi.org/10.1016/j.cellsig.2018.12.004
Li, J., Liu, Q., Liu, Z., et al. (2018) KPNA2 Promotes Metabolic Repro-gramming in Glioblastomas by Regulation of c-myc. Journal of Experimental & Clinical Cancer Research, 37, 194. https://doi.org/10.1186/s13046-018-0861-9
Mayank, A.K., Sharma, S., Deshwal, R.K., et al. (2014) LIMD1 Antagonizes E2F1 Activity and Cell Cycle Progression by Enhancing Rb Function in Cancer Cells. Cell Biology International, 38, 809-817. https://doi.org/10.1002/cbin.10266
Qiao, L., Zhang, Q., Zhang, W., et al. (2018) The Lysine Acetyltransferase GCN5 Contributes to Human papillomavirus Oncoprotein E7-Induced Cell Proliferation via Up-Regulating E2F1. Journal of Cellular and Molecular Medicine, 22, 5333-5345. https://doi.org/10.1111/jcmm.13806
Gao, S., Chen, M., Wei, W., et al. (2018) Crosstalk of mTOR/PKM2 and STAT3/c-Myc Signaling Pathways Regulate the Energy Metabolism and Acidic Microenvironment of Gastric Cancer. Journal of Cellular Biochemistry, 38, 809-817.
Shu, F., Zou, X., Tuo, H., et al. (2019) Stathmin Gene Silencing Suppresses Proliferation, Migration and Invasion of Gastric Cancer Cells via AKT/sCLU and STAT3 Signaling. International Journal of Oncology, 54, 1086-1098.
Chen, W., Li, P., Liu, Y., et al. (2018) Isoalantolactone Induces Apoptosis through ROS-Mediated ER Stress and Inhibition of STAT3 in Prostate Cancer Cells. Journal of Experimental & Clinical Cancer Research, 37, 309. https://doi.org/10.1186/s13046-018-0987-9