Areca nut extract may be a potentially driving force for tumors to become autophagy addicted

We have previously described the mechanisms of action and composition of the autophagy-inducing ingredients found in areca nut (AN). These ingredients are 30-100 kDa molecules present in AN extract (ANE), referred to as ANE 30-100K. In other studies, we demonstrated that chronic stimulation with sub-lethal doses of ANE or ANE 30-100K resulted in increased tolerance to environmental challenges, including serum deprivation, hypoxic conditions, anti-cancer drugs, and accelerated tumor growth in nude mice, through upregulated autophagy activity. Such tumor cells were highly sensitive to the chemical inhibition of autophagy both <i>in vitro</i> and <i>in vivo</i>. Here, we further demonstrated similar inhibitory effects on the growth of stimulated CE81T/VGH cells in mice using <i>atg5</i> shRNA. In contrast, the growth of non-stimulated control cells in mice was shown to be resistant to 3-methyladenine (3-MA). These findings suggest that autophagy blockade might be particularly effective for treating autophagy-dependent tumors in patients with AN-chewing habits.