Autophagy is an evolutionally-conserved catabolic process that degrades damaged organelles, misfolded proteins, and toxic aggregates, reducing oxidative stress. Malfunction of autophagy causes various diseases, including cancer. Autophagy can be either tumor suppressive or promotive. Thus, autophagy modulation is being considered as a new strategy to improve cancer therapy. Areca nut (AN) is a worldwide popular carcinogen and contains apoptosis-inducing ingredients. However, we recently demonstrated that AN may predominantly induce autophagic responses in various types of cells. Furthermore, chronic exposure of cancer cells to this activity generally resulted in increased tolerance against environmental challenges, such as serum starvation, hypoxia, and anti-cancer drugs, through upregulated autophagy activity. We, therefore, propose that AN may have the potential to modulate tumors into an autophagy-addicted manner, raising the possibility of improving cancer therapy through autophagy inhibitionespecially in AN-addicted users.
Ching-Yu Yen, Shyun-Yeu Liu, Mei-Huei Lin, Young-Chau Liu