Pharmacological studies of a novel inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway

The apoptotic mode of cell death (programmed cell death) is an
active and defined process that plays an important role in the
development of multicellular organisms and in the regulation and
maintenance of cell populations in tissues under physiologic and
pathologic conditions. Since dysregulation of apoptosis is
associated with the progress of many diseases, induction of
apoptosis is an interesting pharmacological target for the therapy
of many diseases. Our study shows that the novel semisynthetic
pentacyclic triterpenoid C-KβBA has a profound antiproliferative
effect on different tumor cell lines and that it induces apoptosis
of tumor cells in vitro and vivo. Previous studies have shown that
the mammalian target of rapamycin (mTOR) is a key regulator for
many cells activities, and that the perturbation of this signaling
pathway is implicated in many diseases and metabolic disorders.
Accordingly targeting the mTOR signaling pathway seems to be a
promising therapeutic approach for the treatment of various
diseases and metabolic disorders. We have shown in our study that
C-KβBA downregulates the mTOR signaling pathway in vitro and vivo,
which leads to the induction of cell cycle arrest in the G0 cell
cycle phase as well as downregulation of the protein translation
machinery. Together, the presented data strongly suggest that
C-KβBA could serve as a lead compound for the development of novel
treatment modalities for diseases and disorders associated with
defects in the apoptosis machinery, or the mTOR signaling pathway,
or both.