Open AccessAutophagy modulates the effects of bis‐anthracycline WP 631 on p53‐deficient prostate cancer cells
Author(s) -
Mansilla Sylvia,
Vizcaíno Carolina,
RodríguezSánchez Maria A.,
Priebe Waldemar,
Portugal José
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12402
Subject(s) - autophagy , apoptosis , programmed cell death , cell cycle , microbiology and biotechnology , cytotoxicity , cancer cell , biology , cell cycle checkpoint , cancer research , chemistry , biochemistry , cancer , in vitro , genetics
Treatment of p53‐deficient PC ‐3 human prostate carcinoma cells with nanomolar concentrations of bis‐anthracycline WP 631 induced changes in gene expression, which resulted in G2/M cell cycle arrest, autophagy and cell death. The presence of 2‐deoxy‐D‐glucose (2‐ DG ), which induces metabolic stress and autophagy, enhanced the antiproliferative effects of WP 631. Changes induced by WP 631, 2‐ DG , or co‐treatments with both compounds, in the expression of a variety of genes involved in autophagy and apoptosis were quantified by real‐time PCR . They were consistent with a raise in autophagy followed by cell death. Some cells dying from G2/M phase showed features of necrosis like early changes in membrane permeability, while others were dying by apoptosis that occurred in presence of little caspase‐3 activity. Our results indicate that WP 631 is not only an antiproliferative agent acting on gene transcription, but it can also induce autophagy regardless of the presence of other pro‐autophagy stimuli. The development of autophagy seemed to improve the cytotoxicity of WP 631 in PC ‐3 cells. Our results indicate that autophagy would enhance the activity of DNA ‐binding drugs like WP 631 that are potent inhibitors of gene transcription.