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Open AccessArticle

Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
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Authors to whom correspondence should be addressed.
These authors equally contributed to this work.
These authors contributed equally to this work as senior authors.
Int. J. Mol. Sci. 2019, 20(11), 2613; https://doi.org/10.3390/ijms20112613
Received: 15 April 2019 / Revised: 22 May 2019 / Accepted: 23 May 2019 / Published: 28 May 2019
Acute administration of a high level of extracellular citrate displays an anti-proliferative effect on both in vitro and in vivo models. However, the long-term effect of citrate treatment has not been investigated yet. Here, we address this question in PC3 cells, a prostate-cancer-derived cell line. Acute administration of high levels of extracellular citrate impaired cell adhesion and inhibited the proliferation of PC3 cells, but surviving cells adapted to grow in the chronic presence of 20 mM citrate. Citrate-resistant PC3 cells are significantly less glycolytic than control cells. Moreover, they overexpress short-form, citrate-insensitive phosphofructokinase 1 (PFK1) together with full-length PFK1. In addition, they show traits of mesenchymal-epithelial transition: an increase in E-cadherin and a decrease in vimentin. In comparison with PC3 cells, citrate-resistant cells display morphological changes that involve both microtubule and microfilament organization. This was accompanied by changes in homeostasis and the organization of intracellular organelles. Thus, the mitochondrial network appears fragmented, the Golgi complex is scattered, and the lysosomal compartment is enlarged. Interestingly, citrate-resistant cells produce less total ROS but accumulate more mitochondrial ROS than control cells. Consistently, in citrate-resistant cells, the autophagic pathway is upregulated, possibly sustaining their survival. In conclusion, chronic administration of citrate might select resistant cells, which could jeopardize the benefits of citrate anticancer treatment. View Full-Text
Keywords: citrate; prostate cancer; PC3 cells; cell metabolism; organelle homeostasis; autophagy citrate; prostate cancer; PC3 cells; cell metabolism; organelle homeostasis; autophagy
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MDPI and ACS Style

Caiazza, C.; D’Agostino, M.; Passaro, F.; Faicchia, D.; Mallardo, M.; Paladino, S.; Pierantoni, G.M.; Tramontano, D. Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line. Int. J. Mol. Sci. 2019, 20, 2613. https://doi.org/10.3390/ijms20112613

AMA Style

Caiazza C, D’Agostino M, Passaro F, Faicchia D, Mallardo M, Paladino S, Pierantoni GM, Tramontano D. Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line. International Journal of Molecular Sciences. 2019; 20(11):2613. https://doi.org/10.3390/ijms20112613

Chicago/Turabian Style

Caiazza, Carmen; D’Agostino, Massimo; Passaro, Fabiana; Faicchia, Deriggio; Mallardo, Massimo; Paladino, Simona; Pierantoni, Giovanna M.; Tramontano, Donatella. 2019. "Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line" Int. J. Mol. Sci. 20, no. 11: 2613. https://doi.org/10.3390/ijms20112613

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