PMID- 23404079
OWN - NLM
STAT- MEDLINE
DCOM- 20130819
LR  - 20221207
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 42
IP  - 4
DP  - 2013 Apr
TI  - Protective role of autophagy in matrine‑induced gastric cancer cell death.
PG  - 1417-26
LID - 10.3892/ijo.2013.1817 [doi]
AB  - Matrine has potent antitumor activity against a broad variety of cancer cells and 
      our previous study showed that both autophagy and apoptosis were activated during 
      matrine-induced gastric cancer cell death. The aim of the present study was to 
      determine the significance of autophagy in antineoplastic effects of matrine and 
      the molecular mechanism by which matrine induces autophagy in gastric cancer 
      cells. Western blot analysis showed that exposure of gastric cancer cells to 
      matrine resulted in the extent of autophagy increasing in a dose- and 
      time-dependent manner by detecting micro-tubule-associated protein 1 light chain 
      3 (LC3). This induction was due to activation of autophagic flux, as supported 
      using the lysosome inhibitor, bafilomycin A1, which produced an accumulation of 
      LC3-II. Propidium iodide staining demonstrated that matrine induced cell death in 
      a dose-dependent manner and the autophagy inhibitor 3-methyladenine (3-MA) or 
      bafilomycin A1 enhanced lethality of matrine against gastric cancer cells. 
      Moreover, after pretreatment with 3-MA, some of the gastric cancer cells treated 
      with matrine exhibited prototypical characteristics of apoptosis by transmission 
      electron microscopy. The ability of 3-MA to increase matrine-induced apoptosis 
      was further con fi rmed by Annexin V-FITC/PI staining. Also, the combination of 
      matrine and 3-MA was more potent than matrine alone in inhibiting the 
      proliferation of SGC-7901 cells assessed by sulphorhodamine B assay. Furthermore, 
      administration of the pan-caspase inhibitor zVAD-fmk or autophagy inducer 
      rapamycin decreased the matrine-induced cell death. In addition, matrine 
      treatment did not inhibit the phosphorylation of Akt and its downstream effectors 
      mammalian target of rapamycin (mTOR) as well as p70 ribosomal protein S6 kinase 
      (p70S6K), although the levels of the total Akt and mTOR were decreased. These 
      results suggest that autophagy was activated as a protective mechanism against 
      matrine-induced apoptosis and inhibition of autophagy may be an attractive 
      strategy for enhancing the antitumor potential of matrine in gastric cancer.
FAU - Li, Yumin
AU  - Li Y
AD  - The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China. 
      iym@lzu.edu.cn
FAU - Zhang, Junqiang
AU  - Zhang J
FAU - Ma, Haizhen
AU  - Ma H
FAU - Chen, Xiaohui
AU  - Chen X
FAU - Liu, Tao
AU  - Liu T
FAU - Jiao, Zuoyi
AU  - Jiao Z
FAU - He, Wenting
AU  - He W
FAU - Wang, Furong
AU  - Wang F
FAU - Liu, Xiaokang
AU  - Liu X
FAU - Zeng, Xiangting
AU  - Zeng X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130208
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Alkaloids)
RN  - 0 (Immunoglobulin G)
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (Macrolides)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Quinolizines)
RN  - 0 (antineoplastic agent K 18)
RN  - 5142-23-4 (3-methyladenine)
RN  - 88899-55-2 (bafilomycin A1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - JAC85A2161 (Adenine)
RN  - Q41OR9510P (Melphalan)
RN  - 0 (Matrines)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Alkaloids/*pharmacology
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Cell Line, Tumor/drug effects
MH  - Cell Nucleus/drug effects/pathology
MH  - Cell Shape/drug effects
MH  - Cell Survival/drug effects
MH  - Drug Synergism
MH  - Humans
MH  - Immunoglobulin G/pharmacology
MH  - Macrolides/pharmacology
MH  - Melphalan/pharmacology
MH  - Microtubule-Associated Proteins/metabolism
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Quinolizines/*pharmacology
MH  - Stomach Neoplasms/*drug therapy
MH  - Matrines
EDAT- 2013/02/14 06:00
MHDA- 2013/08/21 06:00
CRDT- 2013/02/14 06:00
PHST- 2012/10/21 00:00 [received]
PHST- 2012/12/07 00:00 [accepted]
PHST- 2013/02/14 06:00 [entrez]
PHST- 2013/02/14 06:00 [pubmed]
PHST- 2013/08/21 06:00 [medline]
AID - 10.3892/ijo.2013.1817 [doi]
PST - ppublish
SO  - Int J Oncol. 2013 Apr;42(4):1417-26. doi: 10.3892/ijo.2013.1817. Epub 2013 Feb 8.