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Intracellular Elemental Patterns of Apoptosis Resistance in Transdifferentiated Androgen-Dependent Prostatic Carcinoma Cells

Published online by Cambridge University Press:  04 August 2016

Mercedes Salido  and
Jose Vilches
Mercedes Salido*
Affiliation:
Department of Histology, Servicio Central de Investigacion Biomedica y en Ciencias de la Salud (SC-IBM), School of Medicine, University of Cadiz, c/Dr. Marañon, 3. 11002 Cádiz, Spain
Jose Vilches
Affiliation:
Department of Histology, Servicio Central de Investigacion Biomedica y en Ciencias de la Salud (SC-IBM), School of Medicine, University of Cadiz, c/Dr. Marañon, 3. 11002 Cádiz, Spain
*
*Corresponding author. [email protected]
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Abstract

The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PC) cells relates to tumor progression and hormone resistance. PC cells may survive and function in androgen-deprived environments, where they could establish paracrine signaling networks, providing stimuli for the propagation of local carcinoma cells. We previously demonstrated, using electron probe X-ray microanalysis (EPXMA), in LNCaP, PC-3, and Du 145 cell lines that apoptosis is associated with intracellular elemental changes, and that the NE secretory products, bombesin and calcitonin, inhibit etoposide-induced apoptosis, as well as some of these elemental changes. In this study, LNCaP cells were induced in vitro to transdifferentiate under androgen deprivation, to mimic the role of NE cells in the apoptotic activity of transdifferentiated androgen-dependent PC cells. Changes in intracellular ion content associated with apoptosis, assessed by EPXMA, demonstrate that the transdifferentiated LNCaP cells are resistant to etoposide-induced apoptosis and also to the etoposide-induced elemental changes. The aggressive malignant potential of PC with neuroendocrine differentiation, associated with hormonal independence, is partly because of the ability that most NE tumor cells have to escape apoptosis, which can enhance the malignant properties of tumor cells and may have therapeutic implications as tumor cells are usually resistant to cytotoxic drugs as etoposide.

Keywords

apoptosisneuroendocrinetransdifferentiationprostate carcinomaion changeselectron probe X-ray microanalysis
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 22 , Issue 4 , August 2016 , pp. 865 - 877
Copyright
© Microscopy Society of America 2016 

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