Methylxanthine derivatives promote autophagy in gastric cancer cells targeting PTEN

Hanyang Liu1, Jun Song, Yan Zhou

  • 1Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China.

Anti-Cancer Drugs
|March 16, 2019
PubMed

Insights

Caffeine and theophylline, methylxanthine derivatives, promote gastric cancer cell death by increasing apoptosis and autophagy. These compounds activate phosphatase and tensin homologue (PTEN), inhibiting the PI3K/Akt/mTOR pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Gastric cancer exhibits suppressed autophagy in tumor tissues compared to adjacent normal tissues.
  • Methylxanthine derivatives like caffeine and theophylline are known to influence apoptosis and autophagy.
  • These compounds reportedly modulate phosphatase and tensin homologue (PTEN) activity and mammalian target of rapamycin (mTOR) signaling.

Purpose of the Study:

  • To investigate the effects of caffeine and theophylline on gastric cancer cell apoptosis and autophagy.
  • To elucidate the role of PTEN in methylxanthine derivative-induced gastric cancer cell death.
  • To evaluate the therapeutic potential of caffeine and theophylline in a gastric cancer model.

Main Methods:

  • Utilized the MGC-803 gastric cancer cell line and a nude mouse model.
  • Assessed apoptosis and autophagy in vitro and in vivo.
  • Employed PTEN knockdown via siRNA transfection to examine pathway involvement.
  • Monitored tumor growth in nude mice treated with methylxanthines and PTEN siRNA.

Main Results:

  • Caffeine and theophylline suppressed MGC-803 cell proliferation and migration while inducing autophagy.
  • PTEN knockdown reversed the inhibitory effects of methylxanthines on the PI3K/Akt/mTOR pathway.
  • Tumor growth was significantly larger in mice treated with PTEN siRNA compared to controls when administered methylxanthines.

Conclusions:

  • Methylxanthine derivatives (caffeine and theophylline) induce gastric cancer cell apoptosis and autophagy.
  • These effects are mediated through PTEN activation and subsequent PI3K/Akt/mTOR pathway suppression.
  • Caffeine and theophylline show promise as potential anticancer therapeutics for gastric cancer.

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