PMID- 33816313
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220421
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Cyclovirobuxine D Induces Apoptosis and Mitochondrial Damage in Glioblastoma 
      Cells Through ROS-Mediated Mitochondrial Translocation of Cofilin.
PG  - 656184
LID - 10.3389/fonc.2021.656184 [doi]
LID - 656184
AB  - BACKGROUND: Cyclovirobuxine D (CVBD), a steroidal alkaloid, has multiple 
      pharmacological activities, including anti-cancer activity. However, the 
      anti-cancer effect of CVBD on glioblastoma (GBM) has seldom been investigated. 
      This study explores the activity of CVBD in inducing apoptosis of GBM cells, and 
      examines the related mechanism in depth. METHODS: GBM cell lines (T98G, U251) and 
      normal human astrocytes (HA) were treated with CVBD. Cell viability was examined 
      by CCK-8 assay, and cell proliferation was evaluated by cell colony formation 
      counts. Apoptosis and mitochondrial superoxide were measured by flow cytometry. 
      All protein expression levels were determined by Western blotting. JC-1 and 
      CM-H(2)DCFDA probes were used to evaluate the mitochondrial membrane potential 
      (MMP) change and intracellular ROS generation, respectively. The cell 
      ultrastructure was observed by transmission electron microscope (TEM). 
      Colocalization of cofilin and mitochondria were determined by immunofluorescence 
      assay. RESULTS: CVBD showed a greater anti-proliferation effect on the GBM cell 
      lines, T98G and U251, than normal human astrocytes in dose- and time-dependent 
      manners. CVBD induced apoptosis and mitochondrial damage in GBM cells. We found 
      that CVBD led to mitochondrial translocation of cofilin. Knockdown of cofilin 
      attenuated CVBD-induced apoptosis and mitochondrial damage. Additionally, the 
      generation of ROS and mitochondrial superoxide was also induced by CVBD in a 
      dose-dependent manner. N-acetyl-L-cysteine (NAC) and mitoquinone (MitoQ) 
      pre-treatment reverted CVBD-induced apoptosis and mitochondrial damage. MitoQ 
      pretreatment was able to block the mitochondrial translocation of cofilin caused 
      by CVBD. CONCLUSIONS: Our data revealed that CVBD induced apoptosis and 
      mitochondrial damage in GBM cells. The underlying mechanism is related to 
      mitochondrial translocation of cofilin caused by mitochondrial oxidant stress.
CI  - Copyright (c) 2021 Zhang, Fu, Duan, Li, Li, Ming, Li, Ni and Chen.
FAU - Zhang, Lin
AU  - Zhang L
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Fu, Ruoqiu
AU  - Fu R
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Duan, Dongyu
AU  - Duan D
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Li, Ziwei
AU  - Li Z
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Li, Bin
AU  - Li B
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Ming, Yue
AU  - Ming Y
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Li, Li
AU  - Li L
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Ni, Rui
AU  - Ni R
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Chen, Jianhong
AU  - Chen J
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20210319
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8018288
OTO - NOTNLM
OT  - apoptosis
OT  - cyclovirobuxine D (CVBD)
OT  - glioblastoma (GBM)
OT  - mitochondrial damage
OT  - oxidative stress
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/04/06 06:00
MHDA- 2021/04/06 06:01
PMCR- 2021/01/01
CRDT- 2021/04/05 06:08
PHST- 2021/01/20 00:00 [received]
PHST- 2021/02/26 00:00 [accepted]
PHST- 2021/04/05 06:08 [entrez]
PHST- 2021/04/06 06:00 [pubmed]
PHST- 2021/04/06 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.656184 [doi]
PST - epublish
SO  - Front Oncol. 2021 Mar 19;11:656184. doi: 10.3389/fonc.2021.656184. eCollection 
      2021.