Dipyridamole impairs autophagic flux and exerts antiproliferative activity on prostate cancer cells.

Dipyridamole impairs autophagic flux and exerts antiproliferative activity on prostate cancer cells. Exp Cell Res. 2019 Jun 10;: Authors: Thomé MP, Pereira LC, Onzi GR, Rohden F, Ilha M, Guma FT, Wink MR, Lenz G Abstract Autophagy is a cellular bulk degradation process used as an alternative source of energy and metabolites and implicated in various diseases. Inefficient autophagy in nutrient-deprived cancer cells would be beneficial for cancer therapy making its modulation valuable as a therapeutic strategy for cancer treatment, especially in combination with chemotherapy. Dipyridamole (DIP) is a vasodilator and antithrombotic drug. Its major effects involve the block of nucleoside uptake and phosphodiestesase inhibition, leading to increased levels of intracellular cAMP. Here we report that DIP increases autophagic markers due to autophagic flux blockage, resembling autophagosome maturation and/or closure impairment. Treatment with DIP results in an increased number of autophagosomes and autolysosomes and impairs degradation of SQSTM1/p62. As blockage of autophagic flux decreases the recycling of cellular components, DIP reduced the intracellular ATP levels in cancer cells. Autophagic flux blockage was neither through inhibition of lysosome function nor blockage of nucleoside uptake, but could be prevented by treatment with a PKA inhibitor, suggesting that autophagic flux failure mediated by DIP results from increased intracellula...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research