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Acta Pharmacol Sin ; 42(5): 780-790, 2021 May.
Article in English | MEDLINE | ID: mdl-32814819

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.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Autophagy/drug effects , Benzofurans/therapeutic use , Morus/chemistry , Neoplasms/drug therapy , Resorcinols/therapeutic use , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Benzofurans/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Endoplasmic Reticulum Stress/drug effects , Female , Humans , Mice, Inbred BALB C , Mice, Nude , Plant Leaves/chemistry , Reactive Oxygen Species/metabolism , Resorcinols/pharmacology , Xenograft Model Antitumor Assays
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