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 in vitro and in vivo. Here, we further demonstrated similar inhibitory effects on the growth of stimulated CE81T/VGH cells in mice using atg5 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.