Betulin inhibits lung carcinoma proliferation through activation of AMPK signaling

Betulin (lup-20(29)-ene-3β, 28-diol) is an abundant, naturally occurring triterpene. It is commonly isolated from the bark of birch trees and forms up to 30% of the dry weight of the extractive. In the present study, we revealed its antiproliferative effects and mechanisms using two lung carcinoma cells (A549 and NCI-292). By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) incorporation assays, we found that betulin could efficiently inhibit cell growth and proliferation. Besides, several key genes of cell-cycle regulators were also affected by betulin treatment. At the molecular level, our results demonstrated that treatment with betulin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in these cells. In agreement, inhibition of AMPK signaling largely reversed the antiproliferative roles of betulin. Taken together, these data provide evidence for a mechanism that may contribute to the antineoplastic effects of betulin and justify further work to explore its potential roles in lung cancer prevention and treatment.