Diterpenoid alkaloids from Aconitum brevicalcaratum as autophagy inducers.

A new C19 diterpenoid alkaloid, brevicanine (1) and six known ones (2-7) were isolated from Aconitum brevicalcaratum (Finet et Gagnep.) Diels. Their structures were elucidated on the basis of extensive spectroscopic analyses. The cytotoxicity of those compounds was investigated against HCT116 human cancer cell line, which showed none of them possessing considerable anti-proliferative activities. To evaluate the autophagy effect of compounds 1-7, Western blot was used to detect the expression of autophagic marker by stimulating human cancer HCT116 cells. The results showed that compound 6 induced protective autophagy in HCT116 cells. Mechanistic insight showed that compound 6 induced protective autophagy through p53 activation, ERK1/2 and p38 MAPK signaling cascade.