Mitochondrial structure alteration in human prostate cancer cells upon initial interaction with a chemopreventive
Chengsen Xue, Hilda A Pasolli, Irene Piscopo
1Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. jen-wei_chiao@nymc.edu.
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.
Insights
Phenethyl isothiocyanate (PEITC), found in cruciferous vegetables, targets mitochondria to inhibit prostate cancer cell growth. This chemopreventive agent disrupts mitochondrial structure and induces apoptosis, offering a novel therapeutic strategy.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Phenethyl isothiocyanate (PEITC) is a natural chemopreventive agent found in cruciferous vegetables.
- PEITC inhibits prostate cancer progression by targeting DNA hypermethylation and histone deacetylases.
- The initial cellular organelle interacting with PEITC remains largely undescribed.
Purpose of the Study:
- To identify the primary cellular organelle targeted by PEITC in human prostate cancer cells.
- To elucidate the early cellular events following PEITC exposure.
Main Methods:
- Human prostate cancer LNCaP cells were treated with PEITC.
- Transmission electron microscopy was used to examine cellular fine structure.
- Mitochondrial membrane potential, cytochrome c release, and apoptosis were assessed.
- Mitochondria were isolated to analyze protein expression.
Main Results:
- PEITC induced significant mitochondrial structural alterations, including condensation and cristae disruption.
- Autophagy markers (smooth endoplasmic reticulum, vacuoles) increased.
- Early apoptotic events, such as cytochrome c release and mitochondrial membrane potential disruption, were observed.
- Reduced expression of mitochondrial outer membrane protein associated with the permeability transition pore was noted.
Conclusions:
- Mitochondria are likely the primary organelle targeted by PEITC.
- PEITC acts as a mitochondria-interacting agent, contributing to its chemopreventive effects against cancer.
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