Abstract
Background
Glioblastoma is a common and lethal primary brain tumor with a mean survival time less than 2 years. Progesterone, a natural steroid hormone, is a small molecule with distinct effects on glioblastoma cells. High concentrations of progesterone more than 10 µM have anti-tumor effects, but the exact mechanism remains unclear.
Objectives
Here, we continually investigate the toxic effects of high-dose progesterone on glioblastoma cells and provide a rationale for using progesterone as a therapeutic drug for glioblastoma treatment.
Results
We observed that high-dose progesterone had consistent inhibitory effect on eight different glioblastoma cell lines. Then, LN-18 and U-87 MG cells were selected for further investigations. Our results demonstrated that high concentrations of progesterone at 25, 50, and 100 µM could trigger extrinsic pathways of apoptosis by upregulating the Fas and Fas ligand. In addition, progesterone in high doses at 25, 50, and 100 µM activated the intrinsic apoptotic pathway by inhibiting anti-apoptotic proteins Bcl-2 and Bcl-xL, and promoting pro-apoptotic proteins Bax and Bak.
Conclusion
These findings suggested that both extrinsic and intrinsic apoptotic pathways contribute to glioblastoma cell apoptosis induced by high concentration of progesterone in vitro.
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Availability of data and material
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Code availability
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (81673689, 81903652 and 82274120), Medical Scientific Research Foundation of Guangdong Province of China (A2022446), Excellent Young Talent Program of GDPH (KY012021187), Scientific Research Funds for High-Level Full-time Talents Introduced by GDPH (KY012021198), and Talent Project established by Chinese Pharmaceutical Association Hospital Pharmacy department (CPA-Z05-ZC-2021-003).
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All the authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Xiao Xiao, Yasi Zhou, Chuyin Peng and Fan Ouyang. The original draft of the manuscript was written by Yasi Zhou and Deli Song. Laiyou Wang contributed to the design of the study, providing critical comments and the editing and correction of the manuscript.
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The author Yasi Zhou declares that she has no conflict of interest. The author Xiao Xiao declares that she has no conflict of interest. The author Chuyin Peng declares that she has no conflict of interest. The author Deli Song declares that he has no conflict of interest. The author Fan Ouyang declares that he has no conflict of interest. The author Laiyou Wang declares that he has no conflict of interest.
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13273_2022_327_MOESM1_ESM.tif
Supplementary file1 (TIF 7046 KB) Supplementary Figure 1.Images of tumor cell after 48 hours treatment with vehicle, progesterone (50 µM) or hydrogen peroxide (1mM) respectively by transmission electron microscopy. Scale bar, 1 μm.
13273_2022_327_MOESM2_ESM.tif
Supplementary file2 (TIF 15744 KB) Supplementary Figure 2. The expression of caspases and its cleaved ones were performed by Western blot in LN-18 and U-87 MG cells after 48 h of incubation with progesterone at different concentrations.
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Zhou, Y., Xiao, X., Peng, C. et al. Progesterone induces glioblastoma cell apoptosis by coactivating extrinsic and intrinsic apoptotic pathways. Mol. Cell. Toxicol. 20, 107–117 (2024). https://doi.org/10.1007/s13273-022-00327-w
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DOI: https://doi.org/10.1007/s13273-022-00327-w