Green tea extract induces protective autophagy in A549 non-small lung cancer cell line.
OBJECTIVE
For many decades, polyphenols, including green tea extract catechins, have been reported to exert multiple anti-tumor activities. However, to date the mechanisms of their action have not been completely elucidated. Thus, the aim of this study was to assess the effect of green tea extract on non-small lung cancer A549 cells.


METHODS
A549 cells following treatment with GTE were analyzed using the inverted light and fluorescence microscope. In order to evaluate cell sensitivity and cell death, the MTT assay and Tali image-based cytometer were used, respectively. Ultrastructural alterations were assessed using a transmission electron microscope.


RESULTS
The obtained data suggested that GTE, even at the highest dose employed (150 μM), was not toxic to A549 cells. Likewise, the treatment with GTE resulted in only a very small dose-dependent increase in the population of apoptotic cells. However, enhanced accumulation of vacuole-like structures in response to GTE was seen at the light and electron microscopic level. Furthermore, an increase in the acidic vesicular organelles and LC3-II puncta formation was observed under the fluorescence microscope, following GTE treatment. The analysis of the functional status of autophagy revealed that GTE-induced autophagy may provide self-protection against its own cytotoxicity, since we observed that the blockage of autophagy by bafilomycin A1 decreased the viability of A549 cells and potentiated necrotic cell death induction in response to GTE treatment.


CONCLUSIONS
Collectively, our results revealed that A549 cells are insensitive to both low and high concentrations of the green tea extract, probably due to the induction of cytoprotective autophagy. These data suggest that a potential utility of GTE in lung cancer therapy may lie in its synergistic combinations with drugs or small molecules that target autophagy, rather than in monotherapy.
Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Magdalena
M
Izdebska
Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Anna
A
Klimaszewska-Wiśniewska
Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Marta
M
Hałas
Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Maciej
M
Gagat
Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Alina
A
Grzanka
D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D002392:Catechin / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D013662:Tea / Q000737:chemistry*
D000975:Antioxidants; D010936:Plant Extracts; D059808:Polyphenols; D013662:Tea; D002392:Catechin