PMID- 29355527
OWN - NLM
STAT- MEDLINE
DCOM- 20180322
LR  - 20180322
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 496
IP  - 4
DP  - 2018 Feb 19
TI  - Isovitexin (IV) induces apoptosis and autophagy in liver cancer cells through 
      endoplasmic reticulum stress.
PG  - 1047-1054
LID - S0006-291X(18)30126-8 [pii]
LID - 10.1016/j.bbrc.2018.01.111 [doi]
AB  - Liver cancer is a leading cause of cancer death worldwide, and novel 
      chemotherapeutic drugs to suppress liver cancer are urgently required. Isovitexin 
      (IV), a glycosylflavonoid, is extracted from rice hulls of Oryza sativa, and has 
      various biological activities. However, the anti-tumor effect of IV against liver 
      cancer has not yet been demonstrated in vitro or in vivo. In the present study, 
      we showed that IV significantly suppressed the growth of liver cancer cells. 
      Mechanistic studies indicated that IV induced apoptosis by the mitochondrial 
      apoptotic pathway, as evidenced by the increase of Bax, cleaved Caspase-3, poly 
      (ADP-ribose) polymerase (PARP), and cytoplasm Cyto-c released from mitochondria. 
      In addition, IV resulted in autophagy in liver cancer cells, supported by the 
      enhancement of LC3II, autophagy-related protein (Atg) 3, Atg5 and Beclin1. 
      Suppressing autophagy using bafilomycin A1 (BFA) or siRNA Atg-5 reduced apoptotic 
      cells in IV-treated cells, demonstrating that autophagy induction regulated 
      apoptosis. Moreover, IV was found to cause endoplasmic reticulum (ER) stress in 
      liver cancer cells, along with the promotion of ER stress-related molecules, 
      including inositol-requiring enzyme 1alpha (IRE1alpha), X-box-binding protein-1s 
      (XBP-1s), C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP)-78. 
      Of note, inhibition of ER stress by use of its inhibitor, tauroursodeoxycholate 
      (TUDCA), significantly reversed IV-induced apoptosis and autophagy. In vivo, IV 
      treatment showed significant tumor growth inhibition compared to the non-treated 
      group. IV could therefore be a strong candidate for liver cancer prevention.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Lv, Sheng-Xiang
AU  - Lv SX
AD  - Department of Gastroenterology, The First People's Hospital of Lianyungang, 
      Xuzhou Medical University Affiliated Hospital of Lianyungang, Lianyungang 222002, 
      China. Electronic address: lvshengxiangxz@foxmail.com.
FAU - Qiao, Xiao
AU  - Qiao X
AD  - Department of Gastroenterology, The Second People's Hospital of Huai'an, Xuzhou 
      Medical University Affiliated Hospital of Huai'an, Huai'an 223000, China.
LA  - eng
PT  - Journal Article
DEP - 20180131
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 7V515PI7F6 (Apigenin)
RN  - KTQ9R9MS0Q (isovitexin)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage
MH  - Apigenin/*administration & dosage
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/pathology/*physiopathology
MH  - Mitochondria, Liver/drug effects/metabolism
MH  - Mitochondrial Proteins/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - ER stress
OT  - Isovitexin
OT  - Liver cancer
EDAT- 2018/01/23 06:00
MHDA- 2018/03/23 06:00
CRDT- 2018/01/23 06:00
PHST- 2018/01/14 00:00 [received]
PHST- 2018/01/17 00:00 [accepted]
PHST- 2018/01/23 06:00 [pubmed]
PHST- 2018/03/23 06:00 [medline]
PHST- 2018/01/23 06:00 [entrez]
AID - S0006-291X(18)30126-8 [pii]
AID - 10.1016/j.bbrc.2018.01.111 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Feb 19;496(4):1047-1054. doi: 
      10.1016/j.bbrc.2018.01.111. Epub 2018 Jan 31.