Cell death & disease, 2018-10, Vol.9 (11), p.1048-13, Article 1048
2018
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Novel dihydroartemisinin derivative DHA-37 induces autophagic cell death through upregulation of HMGB1 in A549 cells
- Ist Teil von
- Cell death & disease, 2018-10, Vol.9 (11), p.1048-13, Article 1048
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Dihydroartemisinin (DHA) and its analogs are reported to possess selective anticancer activity. Here, we reported a novel DHA derivative DHA-37 that exhibited more potent anticancer activity on the cells tested. Distinct from DHA-induced apoptosis, DHA-37 triggered excessive autophagic cell death, and became the main contributor to DHA-37-induced A549 cell death. Incubation of the cells with DHA-37 but not DHA produced increased dots distribution of GFP-LC3 and expression ratio of LC3-II/LC3-I, and enhanced the formation of autophagic vacuoles as revealed by TEM. Treatment with the autophagy inhibitor 3-MA, LY294002, or chloroquine could reverse DHA-37-induced cell death. In addition, DHA-37-induced cell death was associated significantly with the increased expression of HMGB1, and knockdown of HMGB1 could reverse DHA-37-induced cell death. More importantly, the elevated HMGB1 expression induced autophagy through the activation of the MAPK signal but not PI3K-AKT–mTOR pathway. In addition, DHA-37 also showed a wonderful performance in A549 xenograft mice model. These findings suggest that HMGB1 as a target candidate for apoptosis-resistant cancer treatment and artemisinin-based drugs could be used in inducing autophagic cell death.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-4889eISSN: 2041-4889DOI: 10.1038/s41419-018-1006-yTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6189137
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, 13/1, 13/109, 13/2, 13/31, 13/44, 13/89, 13/95, 14/19, 14/28, 14/35, 14/63, 38/22, 45/22, 45/23, 45/44, 45/77, A549 Cells, Adenocarcinoma, Bronchiolo-Alveolar - drug therapy, Adenocarcinoma, Bronchiolo-Alveolar - genetics, Adenocarcinoma, Bronchiolo-Alveolar - metabolism, Adenocarcinoma, Bronchiolo-Alveolar - pathology, AKT protein, Animals, Antibodies, Antineoplastic Agents, Phytogenic - chemical synthesis, Antineoplastic Agents, Phytogenic - pharmacology, Antitumor activity, Apoptosis, Artemisinin, Artemisinins - chemical synthesis, Artemisinins - pharmacology, Autophagy, Autophagy - drug effects, Autophagy - genetics, Biochemistry, Biomedical and Life Sciences, Cancer, Cell Biology, Cell Culture, Cell Cycle - drug effects, Cell Cycle - genetics, Cell death, Chloroquine, Dihydroartemisinin, Drug development, Gene Expression Regulation, Neoplastic, HMGB1 protein, HMGB1 Protein - antagonists & inhibitors, HMGB1 Protein - genetics, HMGB1 Protein - metabolism, Humans, Immunology, Life Sciences, Lung Neoplasms - drug therapy, Lung Neoplasms - genetics, Lung Neoplasms - metabolism, Lung Neoplasms - pathology, Male, MAP kinase, Mice, Mice, Nude, Microtubule-Associated Proteins - genetics, Microtubule-Associated Proteins - metabolism, Mitogen-Activated Protein Kinase 1 - genetics, Mitogen-Activated Protein Kinase 1 - metabolism, Mitogen-Activated Protein Kinase 3 - genetics, Mitogen-Activated Protein Kinase 3 - metabolism, Mitogen-Activated Protein Kinase 8 - genetics, Mitogen-Activated Protein Kinase 8 - metabolism, Phagocytosis, RNA, Small Interfering - genetics, RNA, Small Interfering - metabolism, Signal Transduction, TOR protein, Tumor Burden - drug effects, Vacuoles, Vacuoles - drug effects, Vacuoles - metabolism, Vacuoles - ultrastructure, Xenograft Model Antitumor Assays, Xenografts