PMID- 32767162
OWN - NLM
STAT- MEDLINE
DCOM- 20210910
LR  - 20230526
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 38
IP  - 6
DP  - 2020 Dec
TI  - Glioma progression is suppressed by Naringenin and APO2L combination therapy via 
      the activation of apoptosis in vitro and in vivo.
PG  - 1743-1754
LID - 10.1007/s10637-020-00979-2 [doi]
AB  - Naringenin (NG) is a natural antioxidant flavonoid which is isolated from citrus 
      fruits, and has been reported to inhibit colon cancer proliferation. However, the 
      effects of NG treatment on glioma remain to be elucidated. The present study 
      aimed to explore the effects of NG on glioma in vitro and in vivo. Also, the 
      interactions between NG and APO2 ligand (APO2L; also known as tumor necrosis 
      factor-related apoptosis-inducing ligand) were investigated in glioma. A 
      synergistic effect of NG and APO2L combination on apoptotic induction was 
      observed, though glioma cells were insensitive to APO2L alone. After NG 
      treatment, glioma cells resumed the sensitivity to APO2L and cell apoptosis was 
      induced via the activation of caspases, elevation of decoy receptors 4 and 5 (DR4 
      and DR5) and induction of p53. Coadministration of NG and APO2L decreased levels 
      of anti-apoptotic B cell lymphoma 2 (Bcl-2) family members Bcl-2 and Bcl-extra 
      large (Bcl-xL), while increased levels of proapoptotic factors Bcl-2-associated 
      agonist of cell death (Bad) and Bcl-2 antagonist/killer 1 (Bak). Furthermore, an 
      in vivo mouse xenograft model demonstrated that NG and APO2L cotreatment markedly 
      suppressed glioma growth by activating apoptosis in tumor tissues when compared 
      with NG or APO2L monotherapy. The present study provides a novel therapeutic 
      strategy for glioma by potentiating APO2L-induced apoptosis via the combination 
      with NG in glioma tumor cells.
FAU - Song, Tao
AU  - Song T
AD  - Department of Neurosurgery, Xiangya Hospital of Central South University, 
      Changsha, 410008, Hunan, China.
FAU - Zhang, Mingyu
AU  - Zhang M
AD  - Department of Neurosurgery, Xiangya Hospital of Central South University, 
      Changsha, 410008, Hunan, China.
FAU - Wu, Jun
AU  - Wu J
AD  - Department of Neurosurgery, Xiangya Hospital of Central South University, 
      Changsha, 410008, Hunan, China.
FAU - Chen, Fenghua
AU  - Chen F
AD  - Department of Neurosurgery, Xiangya Hospital of Central South University, 
      Changsha, 410008, Hunan, China.
FAU - Wang, Ying
AU  - Wang Y
AD  - Department of Neurosurgery, Xiangya Hospital of Central South University, 
      Changsha, 410008, Hunan, China.
FAU - Ma, Yujie
AU  - Ma Y
AD  - Department of Neurosurgery, Xiangya Hospital of Central South University, 
      Changsha, 410008, Hunan, China.
FAU - Dai, Zhijie
AU  - Dai Z
AUID- ORCID: 0000-0002-7898-3700
AD  - Department of Metabolism and Endocrinology, National Clinical Research Center for 
      Metabolic Diseases, The Second Xiangya Hospital of Central South University, 139 
      Renmin Middle Road, Changsha, 410011, Hunan, China. daizj2017@csu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200807
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Flavanones)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Mki67 protein, mouse)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Trp53 protein, mouse)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.4.22.- (Caspases)
RN  - HN5425SBF2 (naringenin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Astrocytes/drug effects
MH  - Brain Neoplasms/*drug therapy/metabolism/pathology
MH  - Caspases/metabolism
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Drug Therapy, Combination
MH  - Flavanones/pharmacology/*therapeutic use
MH  - Glioma/*drug therapy/metabolism/pathology
MH  - Humans
MH  - Ki-67 Antigen/metabolism
MH  - Male
MH  - Mice, Nude
MH  - Rats, Sprague-Dawley
MH  - TNF-Related Apoptosis-Inducing Ligand/pharmacology/*therapeutic use
MH  - Tumor Suppressor Protein p53/metabolism
OTO - NOTNLM
OT  - APO2L
OT  - Apoptosis
OT  - Glioma
OT  - Naringenin
EDAT- 2020/08/09 06:00
MHDA- 2021/09/11 06:00
CRDT- 2020/08/09 06:00
PHST- 2020/05/24 00:00 [received]
PHST- 2020/07/31 00:00 [accepted]
PHST- 2020/08/09 06:00 [pubmed]
PHST- 2021/09/11 06:00 [medline]
PHST- 2020/08/09 06:00 [entrez]
AID - 10.1007/s10637-020-00979-2 [pii]
AID - 10.1007/s10637-020-00979-2 [doi]
PST - ppublish
SO  - Invest New Drugs. 2020 Dec;38(6):1743-1754. doi: 10.1007/s10637-020-00979-2. Epub 
      2020 Aug 7.