Autophagy modulates the effects of bis-anthracycline WP631 on p53-deficient prostate cancer cells

作者：Mansilla Sylvia; Vizcaino Carolina; Rodriguez Sanchez Maria A; Priebe Waldemar; Portugal Jose^*

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2015, 19(4): 786-798.

DOI：10.1111/jcmm.12402

• autophagy
• cell death
• PC-3 cells
• Sp1
• WP631

Treatment of p53-deficient PC-3 human prostate carcinoma cells with nanomolar concentrations of bis-anthracycline WP631 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 WP631. Changes induced by WP631, 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 WP631 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 WP631 in PC-3 cells. Our results indicate that autophagy would enhance the activity of DNA-binding drugs like WP631 that are potent inhibitors of gene transcription.

• 出版日期2015-4