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Mitochondrial structure alteration in human prostate cancer cells upon initial interaction with a chemopreventive agent phenethyl isothiocyanate.

Abstract：

BACKGROUND:Phenethyl isothiocyanate (PEITC), present naturally in cruciferous vegetables, is a chemopreventive agent. It blocks initiation and post-initiation progression of carcinogenesis. Mechanism study in human prostate cancer cells revealed that PEITC is a dual inhibitor of aberrant DNA hypermethylation and histone deacetylases, reactivating silenced genes and regulating the androgen-mediated growth of tumor cells. The identity of the cellular organelle that initially interacts with PEITC has not been fully described. METHODS:Human prostate cancer LNCaP cells were exposed to PEITC and the effects on cellular fine structure examined by transmission electron microscopic studies. Alteration of mitochondrial membrane potential and cytochrome c release were evaluated as early events of apoptosis, and the TUNEL method for quantifying apoptotic cells. Mitochondria were isolated for determining their protein expression. RESULTS:Ultrastructural analyses have revealed condensed mitochondria and a perturbed mitochondrial cristae structure, which assumed a rounded and dilated shape within 4-hours of PEITC contact, and became more pronounced with longer PEITC exposure. They presented as the most prominent intracellular alterations in the early hours. Mitochondria structure alterations were demonstrated, for the first time, with the isothiocyanates. An increase in the number of smooth endoplasmic reticulum and vacuoles were also noted that is consistent with the presence of autophagy. Early events of apoptosis were detected, with cytochrome c released along with the appearance of mitochondrial alteration. Mitochondrial membrane potential was disrupted within 18 hours of PEITC exposure, preceding the appearance of apoptotic cells with DNA strand breaks. In parallel, the expression of the mitochondrial class III ß-tubulin in the outer membrane, which associates with the permeability transition pore, was significantly reduced as examined with isolated mitochondria. CONCLUSION:Mitochondria may represent the organelle target of the isothiocyanates, indicating that the isothiocyanates may be mitochondria-interacting agents to inhibit carcinogenesis.

journal_name

Cancer Cell Int

journal_title

Cancer cell international

authors

Xue C,Pasolli HA,Piscopo I,Gros DJ,Liu C,Chen Y,Chiao JW

doi

10.1186/1475-2867-14-30

subject

Has Abstract

pub_date

2014-03-31 00:00:00

pages

issue

issn

1475-2867

pii

1475-2867-14-30

journal_volume

pub_type

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Mitochondrial structure alteration in human prostate cancer cells upon initial interaction with a chemopreventive agent phenethyl isothiocyanate.