Journal
NANOMEDICINE
Volume 14, Issue 3, Pages 335-351Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2018-0330
Keywords
apoptosis; autophagy; doxorubicin; glioblastoma cells; HMGB1; nanodiamonds
Funding
- National Natural Science Foundation of China [81671818]
- Natural Science Foundation of Hubei Province, China [2015CFB403]
- Science and Technology Program of Wuhan, China [2017060201010148]
- Natural Science Foundation of China [31600805]
- Natural Science Foundation of Jiangsu Province [BK20160329]
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Aim: To mechanistically compare the effects of doxorubicin (DOX) and DOX conjugated with nanodiamonds (Nano-DOX) on human glioblastoma cells (GC). 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. 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.
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