Summary:
Purpose: There was time and dose-dependent administration of the factors
oleuropein, adriamycin and their combination on PC-3 cells with the aim of:
Identification of the metabolites involved in the metabolism of cancer cells
and their change after the treatment with these factors. Evaluation of the
their cytostatic action and impact on cell cycle. Investigation of their
mechanism of action by identifying the location and expression of LC3 protein.
Methodology: In this study, PC-3 androgen independent prostate cancer cells
were incubated with the above agents alone and in coadministrationat various
concentrations and chronic effects. The aqueous extracts were analyzed by
nuclear magnetic resonance spectroscopy and identification of metabolites and
statistical analysis methods PCA, PLS-DA and z-score,followed. Also, assays
MTT, study of the cell cycle phases, immunofluorescence and immunoblotting were
carried.
Conclusions: 39 metabolites were identified with those involved in energy
production, building blocks of rapidly dividing tumor cells as well as in
oxidative profile, to star in separating the groups adriamycin, oleuropein,
oleuropein-adriamycin combination and control cells. In coadministration with
adriamycin,oleuropein 200mg/mL, causes great inhibition of proliferation of
cancer cells. The study of the cell cycle revealed induced stop cycle by
adriamycin and the coadministration in phase G2 / M and by oleuropein in phase
G0/G1. Finally, the autophagy was proposed as mechanism of action of the agents
adriamycin and oleuropein, as perinuclear position of LC3 protein and induction
of expression of LC3-II against LC3-I, was observed.
Keywords:
Metabonomics, NMR spectroscopy, Prostate cancer, Oleuropein, Adriamycin
