Aloe-emodin induces autophagy and apoptotic cell death in non-small cell lung cancer cells via Akt/mTOR and MAPK signaling.

Lung cancer has a relatively poor prognosis, and the clinical efficacy of targeted drugs remains unsatisfactory. Therefore, the search for safe and efficient novel antitumor drugs has become an urgent problem in the treatment of lung cancer. Aloe-emodin (AE), a medicinal herb, has been demonstrated to exhibit many pharmacological effects on tumor cells, such as lung cancer cells. However, the anticancer properties of AE have not been fully exploited by modern medicine, as their mechanisms of action are not yet known. In this study, the bioassay results demonstrated that AE reduced the viability of the non-small cell lung cancer cell line A549 and NCI-H1299 in a dose- and time-dependent manner. Moreover, AE induced caspase-dependent apoptosis and autophagy. AE induced autophagy through activation of MAPK signaling and inhibition of the Akt/mTOR pathway. We also found that AE-induced autophagy was attenuated by the reactive oxygen species scavenger N-acetylcysteine, indicating that reactive oxygen species played a key role in AE-mediated autophagy in A549 and NCI-H1299 cells. Furthermore, AE induced reactive oxygen species-dependent autophagy in A549 and NCI-H1299 cells, which triggered apoptosis. Additionally, AE showed synergistic cytotoxic effects with the antitumor drug gemcitabine in A549 and NCI-H1299 cells. In brief, these results showed that AE might be useful for developing a therapeutic candidate for lung cancer complications.