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Published on: May 10, 2016
Phenethyl isothiocyanate-induced cytoskeletal changes and cell death in lung cancer cells
Andrzej Pawlik1, Mariusz Andrzej Szczepanski, Anna Klimaszewska
1Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland. apawlik@onet.eu
Abstract:
Isothiocyanates are known for their anticarcinogenic and antitumor potential, however, the exact mechanism of their action has not been fully elucidated. The present study was designed to investigate and compare the effects of phenethyl isothiocyanate on cell morphology, the cytoskeleton and induction of cell death in human non-small cell lung cancer cell lines A549 and H1299 differing in p53 status. Cell viability tests (MTT assay, xCELLigence system) showed that PEITC exhibits lower cytotoxicity to A549 cells containing wild-type p53. The observed growth-inhibitory effect of PEITC was dose-dependent, but time-dependence was observed only at higher concentrations. The results of flow-cytometric and fluorescence-microscopic analyses indicate that PEITC induced disassembly of actin stress fibers and degradation of tubulin which, most likely, contributed to the induction of cell death. Although, 24-h incubation caused G2/M cell cycle arrest, the fraction of G2/M cells decreased in a dose- and time-dependent manner in favor of cells with sub-G1 DNA content. Further experiments (Annexin V staining, electron microscopic observations) confirmed that the apoptosis-inducing potency of PEITC is probably the main factor responsible for cell growth inhibition. However, PEITC treatment also resulted in the appearance of an increased proportion of H1299 cells exhibiting morphological features of mitotic catastrophe.
Insights
Phenethyl isothiocyanate (PEITC) inhibits lung cancer cell growth by disrupting cell structure and inducing apoptosis. Its effects vary based on p53 status, with less cytotoxicity observed in wild-type p53 cells.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Isothiocyanates possess known anticarcinogenic and antitumor properties.
- The precise mechanisms underlying their action, particularly in lung cancer, require further elucidation.
- Phenethyl isothiocyanate (PEITC) is a compound of interest for its potential therapeutic effects.
Purpose of the Study:
- To investigate and compare the effects of PEITC on human non-small cell lung cancer (NSCLC) cell lines (A549 and H1299) with differing p53 statuses.
- To elucidate the impact of PEITC on cell morphology, cytoskeleton, and the induction of cell death pathways.
- To correlate PEITC's cytotoxic effects with the p53 genetic status of the cancer cells.
Main Methods:
- Cell viability assays (MTT, xCELLigence) were employed to assess cytotoxicity.
- Flow cytometry and fluorescence microscopy were used to analyze cell cycle, apoptosis, and cytoskeletal changes (actin, tubulin).
- Annexin V staining and electron microscopy confirmed apoptosis and morphological changes.
Main Results:
- PEITC demonstrated dose-dependent growth inhibition in both A549 and H1299 cells.
- A549 cells (wild-type p53) exhibited lower cytotoxicity compared to H1299 cells.
- PEITC induced actin stress fiber disassembly, tubulin degradation, G2/M cell cycle arrest, and ultimately apoptosis.
- H1299 cells showed increased features of mitotic catastrophe.
Conclusions:
- PEITC effectively inhibits NSCLC cell growth through cytoskeletal disruption and induction of apoptosis.
- The p53 status influences cellular sensitivity to PEITC, with wild-type p53 conferring relative resistance.
- PEITC's induction of apoptosis is a primary mechanism for its anti-proliferative effects in lung cancer cells.
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