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Nanomedicine (Lond). 2019 Feb;14(3):335-351. doi: 10.2217/nnm-2018-0330. Epub 2019 Jan 24.

Doxorubicin conjugated with nanodiamonds and in free form commit glioblastoma cells to heterodromous fates.

Chen Z1,2, Wang C1,2, Li TF1,2, Li K3, Yue Y1,2, Liu X1,2, Xu HZ1,2, Wen Y1,2, Zhang Q1,2, Han M4, Komatsu N5, Xu YH6, Zhao L7, Chen X1,2.

Author information

1
Department of Pharmacology, School of Basic Medicine, Wuhan University, Donghu Avenue No. 185, Wuhan 430072, China.
2
Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
3
Demonstration Center for Experimental Basic Medicine Education, School of Basic Medicine, Wuhan University, Donghu Avenue No. 185, Wuhan 430072, China.
4
Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
5
Graduate School of Human & Environmental Studies, Kyoto University, Sakyo-Ku, Kyoto 606-8501, Japan.
6
Department of Ophthalmology, Institute of Ophthalmological Research, Renmin Hospital of Wuhan University, Wuhan 430060, China.
7
State Key Laboratory of Radiation Medicine & Protection, School of Radiation Medicine & Protection & School for Radiological & Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu 215123, China.

Abstract

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.

KEYWORDS:

HMGB1; apoptosis; autophagy; doxorubicin; glioblastoma cells; nanodiamonds

PMID:
30676239
DOI:
10.2217/nnm-2018-0330
[Indexed for MEDLINE]

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