Title:The Synthetic Oleanane Triterpenoid HIMOXOL Induces Autophagy in Breast Cancer Cells via ERK1/2 MAPK Pathway and Beclin-1 Up-regulation
Volume: 16
Issue: 8
Author(s): Natalia Lisiak, Ewa Toton, Blazej Rubis, Barbara Majer and Maria Rybczynska
Affiliation:
Keywords:
Oleanolic acid, synthetic triterpenoids, autophagy, breast cancer, Beclin-1, MAPK ERK1/2.
Abstract: Autophagy is engaged in tumor growth and progression, but also acts as a cell death
and tumor suppression initiator. Naturally-derived compounds and their derivatives constitute a
rich source of autophagy modulators.
This paper presents the study on the mechanism of action of oleanolic acid derivatives,
HIMOXOL and Br-HIMOLID, in MCF7 breast cancer cells. Both compounds reduced MCF7
cell viability more efficiently than the parental compound. It is noteworthy that this effect was
specific to MCF7 cancer cells, while in non-cancer MCF-12A cells the cytotoxicity of the
studied compounds was significantly lower. Moreover, in contrast to oleanolic acid, the tested
compounds were only able to increase autophagy in MCF7 cells. Interestingly, HIMOXOL
caused a significantly (p<0.05) higher autophagy rate in MCF7 cells than Br-HIMOLID, as
measured by an LC3 immuno-identification study. We also found that HIMOXOL upregulated
Beclin-1 expression in MCF7 cells. The observed biological activity of the compound
contributed to the modulation of the MAPK ERK1/2 pathway that is engaged in the regulation of autophagy signaling.
Importantly, we revealed no proapoptotic activity of the compound in the studied cells. However, autophagy induction
in MCF7 cancer cells was reflected in the significantly decreased viability of these cells. Thus, we conclude that
HIMOXOL (but not Br-HIMOLID) might reveal a significant potential against breast cancer cells, since it might
efficiently induce the main autophagy mediator and prognostic factor, BECN1.
