PT  - JOURNAL ARTICLE
AU  - CHANG-TA CHIU
AU  - SHYUN-YEU LIU
AU  - CHING-YU YEN
AU  - BANG-YEN LIU
AU  - ZI-YU SUN
AU  - CHUN-YI WU
AU  - JI-LUNG DENG
AU  - YOUNG-CHAU LIU
AU  - MEI-HUEI LIN
TI  - Chronic Stimulation of the Autophagy-inducing Ingredient of Areca Nut Promotes Tumor Growth <em>In Vivo</em> Through Up-regulation of Tumoral Autophagy
AID  - 10.21873/anticanres.13943
DP  - 2020 Jan 01
TA  - Anticancer Research
PG  - 221--227
VI  - 40
IP  - 1
4099  - http://ar.iiarjournals.org/content/40/1/221.short
4100  - http://ar.iiarjournals.org/content/40/1/221.full
SO  - Anticancer Res2020 Jan 01; 40
AB  - 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 microtubule-associated 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.