Chronic stimulation of the autophagy-inducing ingredient of areca nut promotes tumor growth in vivo through up-regulation of tumoral autophagy

Chang Ta Chiu, Shyun Yeu Liu, Ching Yu Yen, Bang Yen Liu, Zi Yu Sun, Chun Yi Wu, Ji Lung Deng, Young Chau Liu, Mei Huei Lin

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Background/aim: Autophagy can be either tumor promotive or suppressive. We previously identified an autophagy-inducing activity in the 30-100 kDa fraction of areca-nut-extract (ANE 30-100K) and showed that several tumor cells subjected to chronic ANE 30-100K stimulation (CAS) exhibited higher resistance against stressed environments including serum-free (SF) conditions in vitro. Herein, we aimed to assess whether CAS can also provide growth advantages for tumor cells in vivo and the therapeutic effect of autophagy inhibition on CAS-treated tumors. Materials and Methods: Esophageal CE81T/VGH cells and nude mice were used as experimental models. Autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ), as well as another anticancer drug cisplatin (DDP), were chosen to challenge CAS-treated CE81T/VGH cells in vitro and in vivo. Results: CAS-treated CE81T/VGH cells expressed higher levels of microtubuleassociated protein 1 light chain 3A/B-II (LC3-II) and beclin 1 proteins, and showed stronger resistance to SF and hypoxia conditions, that were mitigated by CQ or 3-MA in vitro. Furthermore, CAS-treated CE81T/VGH cells induced significantly larger tumors in mice, which were also attenuated by single 3-MA or CQ treatment. Finally, the combined treatment of 3-MA or CQ with DDP further up-regulated DDP-induced caspase-3 activity in vitro and exhibited synergistic anti-tumor effects on mice. Conclusion: CAS may up-regulate tumoral autophagy and provide growth advantage for tumors both in vitro and in vivo. Furthermore, autophagy inhibition alone or in combination with DDP may achieve positive therapy for tumors encountered with CAS.
Original languageEnglish
Pages (from-to)221-227
Number of pages7
JournalAnticancer Research
Issue number1
Publication statusPublished - Jan 1 2020


  • 3-methyladenine
  • Areca nut
  • Autophagy
  • Chloroquine
  • Cisplatin
  • Nude mice
  • Areca/chemistry
  • Up-Regulation
  • Neoplasms/pathology
  • Cell Proliferation
  • Humans
  • Male
  • Nuts/chemistry
  • Animals
  • Autophagy/genetics
  • Mice, Nude
  • Cell Line, Tumor
  • Cell Hypoxia/genetics
  • Mice, Inbred BALB C

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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