ReferenceID 5533

Anti-tumor effects of jaceosidin on apoptosis, autophagy, and necroptosis in human glioblastoma multiforme

Am J Cancer Res

Glioblastoma multiforme (GBM) is the most aggressive and common malignant neoplasm. Nevertheless, a 5-year survival rate of patients with GBM has remained below 5%. Artemisia princeps PAMPANINI, used as a food and tradit

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Reference Id
5533
Evidence Id
22123
Core Evidence Id
22123
Source Reference Id
4298
Herb2 Reference Id
HBREF005095
Subject Paper Key
HBIN031409_34765300
Pubmed Id
34765300
Doi
Paper Title
Anti-tumor effects of jaceosidin on apoptosis, autophagy, and necroptosis in human glioblastoma multiforme
Paper Abstract
Glioblastoma multiforme (GBM) is the most aggressive and common malignant neoplasm. Nevertheless, a 5-year survival rate of patients with GBM has remained below 5%. Artemisia princeps PAMPANINI, used as a food and traditional medicine, have shown beneficial properties including anti-inflammatory, anti-oxidative, and anti-cancer activities. Thus, this study aimed to investigate biological mechanism of a bioactive compound, jaceosidin (JAC), isolated from A. princeps in human GBM T98G cells. Herein, as a result of analysis in terms of cancer survival and death, we found that JAC significantly reduced cell survival against T98G cells. In addition, JAC increased apoptotic cell death via changes on morphological and molecular phenotypes in T98G cells as evidenced by cellular shapes and DNA fragmentation. The apoptotic cell death was confirmed by the cleavage of caspase-3 and PARP, the downregulation of survivin and Bcl-2. Moreover, JAC decreased the expression of cyclinD1 and Cdks and increased the phosphorylation of EKR, JNK, and p38 MAPKs. Specifically, JAC suppressed the PI3K/AKT signaling and its downstream molecules including p70S6, GSK3beta, and beta-catenin. In addition, as a result of analysis in terms of metastasis using wound healing and Boyden chamber assays, JAC showed anti-migrative and anti-invasive activities. Finally, we analyzed in terms of autophagy and necroptosis that are modes of programmed cell survival and death different from apoptosis in T98G cells. We found that JAC inhibited autophgic regulatory proteins including Beclin-1, Atgs, and LC3A/B, thereby reducing autophagic-mediated cell survival, whereas JAC did not affect phosphorylation of key proteins in necroptosis, especially MLKL. Given these findings, our results provided novel evidences on the biological mechanisms of JAC in T98G cells, suggesting that JAC may be a therapeutic agent for patients with GBM.
Journal
Am J Cancer Res
Publish Year
2021
Experiment Subject
human; patient; human gbm t98g cells; t98g cells
Experiment Type
Cell Experiment
Phenotype Related
Malignant Neoplasm; Glioblastoma Multiforme; Cancer
Paper Title Cn
Paper Title En
Anti-tumor effects of jaceosidin on apoptosis, autophagy, and necroptosis in human glioblastoma multiforme
Bilingual Status
semi_complete