PMID- 26449828
OWN - NLM
STAT- MEDLINE
DCOM- 20170207
LR  - 20181113
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 37
IP  - 3
DP  - 2016 Mar
TI  - Hesperetin induces apoptosis of esophageal cancer cells via mitochondrial pathway 
      mediated by the increased intracellular reactive oxygen species.
PG  - 3451-9
LID - 10.1007/s13277-015-4176-6 [doi]
AB  - Esophageal cancer is of high prevalence and poor prognosis. Hesperetin has been 
      reported to exert antitumor ability by inducing apoptosis in many cancers in 
      vitro and in vivo without obvious toxicity. However, there is no study concerning 
      about the effect of hesperetin on esophageal cancer. In this study, we aimed to 
      investigate whether hesperetin could induce apoptosis in esophageal cancer cells 
      and explore its potential mechanism. We found that hesperetin induced esophageal 
      cancer cells apoptosis in a concentration-dependent and time-dependent manner 
      compared with the untreated cells. Hoechst 33258 staining and flow cytometry 
      analysis showed more apoptotic cells in the hesperetin-treated group (p < 0.05, 
      respectively). The intracellular reactive oxygen species (ROS) increased 
      significantly, and glutathione (GSH) was depleted. The loss of  big up tri, openPsi m was more 
      tremendous in the hesperetin-treated cells. N-acetylcysteine (NAC) reduced the 
      proapoptotic ability of hesperetin, while DL-buthionine-S, R-sulfoximine (BSO) 
      enhanced the anticancer effect. Western blotting showed that the expression 
      levels of cytochrome C (Cyt C) and apoptosis-inducing factor (AIF) decreased in 
      mitochondria and increased in cytoplasm (p < 0.05). The levels of intracellular 
      cleaved caspase-9, cleaved caspase-3, Apaf-1, Bcl-2-associated X protein (Bax), 
      and suppressor of fused (SuFu) increased, while B cell lymphoma 2 (Bcl-2) and 
      Survivin decreased. What is more, in xenograft tumor model, hesperetin inhibited 
      the tumor growth significantly via induction of cell apoptosis which was detected 
      by TUNEL assay (p < 0.05). Taken together, our study demonstrated that hesperetin 
      could induce cell apoptosis in esophageal cancer cells via mitochondrial-mediated 
      intrinsic pathway by accumulation of ROS.
FAU - Wu, Dandan
AU  - Wu D
AD  - Department of Gastroenterology, Renmin Hospital of Wuhan University, 238# Jiefang 
      Road, Wuhan, Hubei Province, China.
FAU - Zhang, Jixiang
AU  - Zhang J
AD  - Department of Gastroenterology, Renmin Hospital of Wuhan University, 238# Jiefang 
      Road, Wuhan, Hubei Province, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Gastroenterology, Renmin Hospital of Wuhan University, 238# Jiefang 
      Road, Wuhan, Hubei Province, China.
FAU - Li, Jiao
AU  - Li J
AD  - Department of Gastroenterology, Renmin Hospital of Wuhan University, 238# Jiefang 
      Road, Wuhan, Hubei Province, China.
FAU - Liao, Fei
AU  - Liao F
AD  - Department of Gastroenterology, Renmin Hospital of Wuhan University, 238# Jiefang 
      Road, Wuhan, Hubei Province, China.
FAU - Dong, Weiguo
AU  - Dong W
AD  - Department of Gastroenterology, Renmin Hospital of Wuhan University, 238# Jiefang 
      Road, Wuhan, Hubei Province, China. dwg@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20151008
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - E750O06Y6O (Hesperidin)
RN  - GAN16C9B8O (Glutathione)
RN  - Q9Q3D557F1 (hesperetin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Esophageal Neoplasms/*drug therapy/metabolism/pathology
MH  - Female
MH  - Glutathione/metabolism
MH  - Hesperidin/*pharmacology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mitochondria/*physiology
MH  - Proto-Oncogene Proteins c-bcl-2/analysis
MH  - Reactive Oxygen Species/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Esophageal cancer
OT  - Hesperetin
OT  - Mitochondrial pathway
OT  - ROS
EDAT- 2015/10/10 06:00
MHDA- 2017/02/09 06:00
CRDT- 2015/10/10 06:00
PHST- 2015/08/27 00:00 [received]
PHST- 2015/09/28 00:00 [accepted]
PHST- 2015/10/10 06:00 [entrez]
PHST- 2015/10/10 06:00 [pubmed]
PHST- 2017/02/09 06:00 [medline]
AID - 10.1007/s13277-015-4176-6 [pii]
AID - 10.1007/s13277-015-4176-6 [doi]
PST - ppublish
SO  - Tumour Biol. 2016 Mar;37(3):3451-9. doi: 10.1007/s13277-015-4176-6. Epub 2015 Oct 
      8.