6-Methyl-1-(3-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3- c]pyridin-4(5H)-one (FMPPP) exhibits anti-proliferative effect on prostate cancer via autophagy induction and mTOR/p70S6K inhibition
Purpose: To investigate 6-methyl-1-(3-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3-c]pyridin-4(5H)-one (FMPPP) as anti-proliferative agent against prostate cancers.
Methods: The FMPPP-mediated changes in cell proliferation were measured using cell counting kit-8 (CCK-8). Flow cytometry and propidium iodide staining were used for cellular DNA content determination. Proteins expression in cells was probed by western blotting assay.
Results: A significant (p < 0.05) dose-dependent suppression of DU145 and PC 3 cell proliferation was observed following FMPPP treatment. FMPPP treatment at 20 μM raised DU145 cell fraction to 75.08 ± 4.87 % in G1 phase when compared to 48.32 ± 3.44 % for control. The population of PC 3 cells in G1- phase reached to 72.78 ± 5.21 % on treatment with 20 μM FMPPP compared to 49.65 ± 4.62 % in control. The FMPPP treatment of DU145 and PC-3 cells elevated LC3-II expression and suppressed SQSTM1/p62 expression. In FMPPP-treated DU145 and PC-3 cells, p-ERK1/2 level was promoted whereas mTOR and p70S6K phosphorylation significantly decreased. Exposure to U0126 (ERK pathway inhibitor) reduced FMPPP-induced increase of LC3-II expression and promotion of p-ERK1/2 level in DU145 and PC-3 cells.
Conclusion: FMPPP exhibits anti-proliferative effect by increasing autophagy in prostate cancer cells. The cytotoxicity of FMPPP involves elevation of ERK1/2 phosphorylation and targeting mTOR pathway in DU145 and PC-3 cells. Therefore, FMPPP may be beneficial for the treatment of prostate cancer in patients.
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.