Abstract
A new pimarane-type diterpene, ent-8(14),15-pimaradiene-2β,19-diol (JXE-23), was isolated from the fern plant Aleuritopteris albofusca by our previous work; however, the biological activity of this diterpene remains unclear. In the present study, the anti-cancer potential of JXE-23 in various cancer cells was investigated. Among MCF-7 breast cancer cells, A549 lung cancer cells, and HepG2 liver cancer cells, JXE-23 displayed significant cytotoxicity to HepG2 cells with an IC50 value of 17.20 ± 1.73 µM, while showing no obvious toxicity in normal hepatocytes HL7702. JXE-23 inhibited cell growth and colony formation in HepG2 cells. A cell cycle distribution analysis showed that JXE-23 caused G2/M cell cycle arrest. Besides, JXE-23 also suppressed the migration of HepG2 cells. Interestingly, an increase of light chain 3 II (LC3II) and Beclin 1 and a decrease of P62 have occurred in JXE-23-treated cells, as well as the formation of GFP-LC3 dots, indicative of autophagy induction by JXE-23. When combined with autophagy inhibitor 3-methyladenine and chloroquine, the cell viability was significantly reduced, suggesting that JXE-23 triggered protective autophagy in hepatoma cells. Further study showed that JXE-23 inactivated the CIP2A/p-AKT/c-Myc signaling axis in HepG2 cells. Our data provided evidence that JXE-23 inhibited cell growth, arrested cells at the G2/M phase, and induced protective autophagy in HepG2 hepatocellular carcinoma cells. JXE-23 may be a potential lead compound for anti-cancer drug development, and autophagy inhibitor treatment may provide an effective strategy for improving its anti-cancer effect.
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Funding
This project was supported by Anhui Provincial Natural Science Foundation (2008085MH292), the Key Program in the Youth Elite Support Plan in Universities of Anhui Province (gxyqZD2019020 and gxyqZD2020016), National Natural Science Foundation of China (81872449), and the Student Research and Training Program of Anhui University of Technology (S202210360211).
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Liang Ma and Guozheng Huang conceived and designed research. Yumeng Zhang, Fuchun Wang, Jian Liu and Yu Zhang conducted experiments. Jianguo Cao and Guozheng Huang provided the compound JXE-23. Yumeng Zhang, Zi Liu and Liang Ma analyzed data. Zi Liu, Guozheng Huang and Liang Ma wrote the manuscript. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Zhang, Y., Liu, Z., Wang, F. et al. ent-8(14),15-Pimaradiene-2β,19-diol, a diterpene from Aleuritopteris albofusca, inhibits growth and induces protective autophagy in hepatocellular carcinoma cells. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03048-0
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DOI: https://doi.org/10.1007/s00210-024-03048-0