Abstract
Guangsangon E (GSE) is a novel Diels–Alder adduct isolated from leaves of Morus alba L, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP–LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as “autophagy-mediated cell death.” Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.
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Acknowledgements
This work was supported by the National Science and Technology Major Project of China (2019ZX09301004), Zhejiang Provincial Science and Technology Planning Project (2016C04005) to JKT; Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program, Zhejiang Provincial Qianjiang Talents Program, Zhejiang Provincial Natural Science Foundation (LR18H160002), Traditional Chinese Medicine Scientific Research Fund Project of Zhejiang Province (2018ZB010), Zhejiang Provincial Program in Medicine and Health Sciences and Technology (2018253645) to JBZ; National Natural Science Foundation of China (81703907) to XS; Zhejiang Provincial Program in Medicine and Health Sciences and Technology (2018KY223) to SFY.
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JBZ and JKT designed research; HHY, YHS, CCG, and MTX performed research; RLG and SFY contributed new reagents or analytic tools; YTH, XS, and SXL analyzed data; HHY and YHS wrote the paper; HTH and ZPW drafted the rebutal letter.
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Shu, Yh., Yuan, Hh., Xu, Mt. et al. A novel Diels–Alder adduct of mulberry leaves exerts anticancer effect through autophagy-mediated cell death. Acta Pharmacol Sin 42, 780–790 (2021). https://doi.org/10.1038/s41401-020-0492-5
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DOI: https://doi.org/10.1038/s41401-020-0492-5
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