PMID- 28101201
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220311
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 12
IP  - 6
DP  - 2016 Dec
TI  - Diosmetin inhibits cell proliferation and induces apoptosis by regulating 
      autophagy via the mammalian target of rapamycin pathway in hepatocellular 
      carcinoma HepG2 cells.
PG  - 4385-4392
LID - 10.3892/ol.2016.5301 [doi]
AB  - Hepatocellular carcinoma (HCC), which is a type of malignant tumor, is the fifth 
      most common cancer in men and ninth in women worldwide. The aim of the present 
      study was to investigate the antitumor effect of diosmetin (DIOS) in 
      hepatocellular carcinoma HepG2 cells. The proliferation, apoptosis and autophagy 
      rates of HepG2 cells were measured following treatment with DIOS. The effects of 
      DIOS treatment on HepG2 cell proliferation and apoptosis rates were analyzed 
      using MTT assays and Annexin V staining, respectively. The effect of DIOS 
      treatment on autophagy levels was assessed using transmission electron 
      microscopy, green fluorescent protein (GFP)-microtubule-associated protein 1 
      light chain (LC3) transfection and LysoTracker Red staining. Furthermore, 
      bafilomycin A1 (BA1), an autophagy inhibitor, was used to assess the association 
      between DIOS and cell autophagy, proliferation and apoptosis. In addition, the 
      expression of autophagy-related proteins [mammalian target of rapamycin (mTOR), 
      phosphatidylinositol 3-kinase, P70S6K, phosphoinositide-dependent kinase-1, 
      extracellular signal-regulated kinase, 5'-AMP-activated protein kinase and Akt] 
      and apoptosis-related proteins [B-cell lymphoma (Bcl)-2-associated X protein, 
      Bak, p53, Bcl-2 and caspase-3] were analyzed by western blotting. The results 
      revealed that DIOS significantly inhibited proliferation (P<0.01) and induced 
      apoptosis (P<0.001) in HepG2 cells. It was also demonstrated that DIOS triggered 
      autophagy by regulating the mTOR pathway in HepG2 cells. Notably, following 
      treatment of HepG2 cells with the autophagy inhibitor, BA1, the expression of 
      apoptosis-related proteins, including Bax, Bak and p53, were significantly 
      decreased (P<0.05), and cell viability was recovered to a certain extent. In 
      conclusion, DIOS inhibits cell proliferation and induces apoptosis in HepG2 cells 
      via regulation of the mTOR pathway. Thus, the results of the current study 
      indicate that DIOS may present a potential therapeutic agent for HCC treatment.
FAU - Liu, Jie
AU  - Liu J
AD  - Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical 
      University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, 
      Guangdong 524001, P.R. China.
FAU - Ren, Hao
AU  - Ren H
AD  - Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical 
      University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, 
      Guangdong 524001, P.R. China.
FAU - Liu, Bin
AU  - Liu B
AD  - Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical 
      University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, 
      Guangdong 524001, P.R. China.
FAU - Zhang, Qingyu
AU  - Zhang Q
AD  - Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical 
      University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, 
      Guangdong 524001, P.R. China.
FAU - Li, Mingyi
AU  - Li M
AD  - Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical 
      University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, 
      Guangdong 524001, P.R. China.
FAU - Zhu, Runzhi
AU  - Zhu R
AD  - Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical 
      University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, 
      Guangdong 524001, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20161019
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC5228182
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - diosmetin
OT  - hepatocellular carcinoma
OT  - mammalian target of rapamycin
EDAT- 2017/01/20 06:00
MHDA- 2017/01/20 06:01
PMCR- 2016/10/19
CRDT- 2017/01/20 06:00
PHST- 2015/08/24 00:00 [received]
PHST- 2016/08/26 00:00 [accepted]
PHST- 2017/01/20 06:00 [entrez]
PHST- 2017/01/20 06:00 [pubmed]
PHST- 2017/01/20 06:01 [medline]
PHST- 2016/10/19 00:00 [pmc-release]
AID - OL-0-0-5301 [pii]
AID - 10.3892/ol.2016.5301 [doi]
PST - ppublish
SO  - Oncol Lett. 2016 Dec;12(6):4385-4392. doi: 10.3892/ol.2016.5301. Epub 2016 Oct 
      19.