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Doxorubicin conjugated with nanodiamonds and in free form commit glioblastoma cells to heterodromous fates.
- Source :
-
Nanomedicine (London, England) [Nanomedicine (Lond)] 2019 Feb; Vol. 14 (3), pp. 335-351. Date of Electronic Publication: 2019 Jan 24. - Publication Year :
- 2019
-
Abstract
- Aim: To mechanistically compare the effects of doxorubicin (DOX) and DOX conjugated with nanodiamonds (Nano-DOX) on human glioblastoma cells (GC).<br />Materials & Methods: GC viablity, proliferation and activation of apoptosis and autophagy was assayed in response to DOX and Nano-DOX. Expression and release of HMGB1 were measured and its role in apoptosis and autophagy probed in response to DOX and Nano-DOX.  Results: DOX induced apoptosis in GC while Nano-DOX induced autophagy. Inhibition of autophagy in Nano-DOX-treated GC promoted apoptosis. DOX suppressed the emission of HMGB1 while Nano-DOX stimulated HMGB1 emission which was attenuated when autophagy was repressed. Blocking of HMGB1 emission mitigated autophagy and enhanced apoptosis in Nano-DOX-treated GC. Exogenously administered HMGB1 promoted autophagy and protected against apoptosis in both Nano-DOX-treated GC and DOX-treated GC.<br />Conclusions: Nano-DOX is a potent autophagy activator as opposed to DOX as an apoptosis inducer. Nano-DOX initiates a mutual reinforcement loop between autophagy and HMGB1 in GC and thereby protects GC against apoptosis.
Details
- Language :
- English
- ISSN :
- 1748-6963
- Volume :
- 14
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nanomedicine (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 30676239
- Full Text :
- https://doi.org/10.2217/nnm-2018-0330