PMID- 30875347
OWN - NLM
STAT- MEDLINE
DCOM- 20200909
LR  - 20211204
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 30
IP  - 4
DP  - 2019 Apr
TI  - Methylxanthine derivatives promote autophagy in gastric cancer cells targeting 
      PTEN.
PG  - 347-355
LID - 10.1097/CAD.0000000000000724 [doi]
AB  - Methylxanthine derivatives, such as caffeine and theophylline, enhance cell 
      apoptosis and autophagy and reportedly induce the activity of phosphatase and 
      tensin homologue (PTEN) and inhibit the mammalian target of rapamycin (mTOR). 
      This study investigated the impacts of caffeine and theophylline on gastric 
      cancer cell apoptosis and autophagy using a gastric cancer cell line (MGC-803) 
      and a nude mouse model. Peritumoural and tumour tissues were collected from five 
      patients diagnosed with gastric carcinoma who underwent laparoscopic radical 
      gastrectomy at our hospital. Autophagy was suppressed in gastric cancer tumour 
      tissue compared with peritumoural tissue. In vitro, both caffeine and 
      theophylline effectively suppressed MGC-803 cell proliferation and migration and 
      induced autophagy. To assess the involvement of PTEN in caffeine-mediated and 
      theophylline-mediated gastric cancer cell death, we transiently transfected 
      MGC-803 cells with an siRNA targeting PTEN. PTEN knockdown impaired the 
      methylxanthine derivative-mediated inhibition of PI3K/Akt/mTOR signalling. In 
      nude mice treated with caffeine or theophylline, MGC-803 cell tumours injected 
      with siPTEN were larger than those injected with negative control siRNA. These 
      results show that the methylxanthine derivatives (caffeine and theophylline) 
      effectively induce gastric cancer cell apoptosis and autophagy by PTEN activation 
      and PI3K/Akt/mTOR pathway suppression and strongly support the use of 
      methylxanthine derivatives as potential anticancer therapeutics.
FAU - Liu, Hanyang
AU  - Liu H
AD  - Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's 
      Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China.
FAU - Song, Jun
AU  - Song J
FAU - Zhou, Yan
AU  - Zhou Y
FAU - Cao, Liang
AU  - Cao L
FAU - Gong, Yu
AU  - Gong Y
FAU - Wei, Yi
AU  - Wei Y
FAU - Yang, Haojun
AU  - Yang H
FAU - Tang, Liming
AU  - Tang L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Xanthines)
RN  - 28109-92-4 (methylxanthine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - *Autophagy
MH  - Cell Proliferation
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - PTEN Phosphohydrolase/*antagonists & inhibitors/metabolism
MH  - Prognosis
MH  - Signal Transduction
MH  - Stomach Neoplasms/drug therapy/metabolism/*pathology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Cells, Cultured
MH  - Xanthines/*chemistry/*pharmacology
MH  - Xenograft Model Antitumor Assays
EDAT- 2019/03/16 06:00
MHDA- 2020/09/10 06:00
CRDT- 2019/03/16 06:00
PHST- 2019/03/16 06:00 [entrez]
PHST- 2019/03/16 06:00 [pubmed]
PHST- 2020/09/10 06:00 [medline]
AID - 00001813-201904000-00004 [pii]
AID - 10.1097/CAD.0000000000000724 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2019 Apr;30(4):347-355. doi: 10.1097/CAD.0000000000000724.