Epigallocatechin gallate and thermal cycling-stimulation synergistically promote apoptosis in A549 cells via endoplasmic reticulum stress-induced calcium ion dysregulation and oxidative stress
- 1Department of Physics, Laboratory for Medical Physics and Biomedical Engineering, National Taiwan University, Taipei 106319, Taiwan, R.O.C.
- 2Molecular Imaging Center, National Taiwan University College of Medicine, Taipei 100233, Taiwan, R.O.C.
- 3Graduate Institute of Applied Physics, Biophysics Division, National Taiwan University, Taipei 106319, Taiwan, R.O.C.
Abstract
Non-small cell lung cancer (NSCLC), as the predominant subtype of lung cancer, presents a considerable clinical challenge due to its high rates of recurrence and the significant adverse effects associated with conventional therapeutic modalities. In response to these challenges, the present study has explored the combined anticancer effects of epigallocatechin gallate (EGCG) together with thermal cycling-stimulation (TCS). The findings obtained demonstrated that the combination of EGCG and TCS led to a synergistic decrease in the viability of A549 and NCI-H460 NSCLC cells, whereas IMR-90 normal lung fibroblasts exhibited minimal cytotoxic effects. Further investigations revealed that EGCG could mitigate the TCS-induced upregulation of the heat shock proteins (HSPs) HSP70 and HSP105, whereas the expression levels of proteasome subunits were concurrently decreased. These alterations were accompanied by the disruption of proteostasis, and also by the activation of endoplasmic reticulum (ER) stress-associated pathways. Furthermore, pharmacological inhibition studies suggested a mutual interplay between inositol 1,4,5-trisphosphate receptor-mediated ER Ca2+ release and an excessive production of reactive oxygen species, ultimately causing the cells to undergo mitochondrial apoptosis. In summary, the present study has shown that the combined treatment of EGCG and TCS reduces the required dosage of EGCG, while also attenuating TCS-induced heat shock responses. Consequently, the present study offers a novel and promising in vitro proof-of-concept strategy for treating NSCLC.
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BibTeX
@article{hsu2026epigallocatechin,
title = {{Epigallocatechin gallate and thermal cycling-stimulation synergistically promote apoptosis in A549 cells via endoplasmic reticulum stress-induced calcium ion dysregulation and oxidative stress}},
author = {Fang-Tzu Hsu and Hsu-Hsiang Liu and Yi Kung and Chieh-Jou Lin and Chih-Yu Chao},
journal = {Molecular Medicine Reports},
year = {2026},
month = oct,
doi = {10.3892/mmr.2026.14043},
url = {https://doi.org/10.3892/mmr.2026.14043},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Epigallocatechin gallate and thermal cycling-stimulation synergistically promote apoptosis in A549 cells via endoplasmic reticulum stress-induced calcium ion dysregulation and oxidative stress
AU - Fang-Tzu Hsu
AU - Hsu-Hsiang Liu
AU - Yi Kung
AU - Chieh-Jou Lin
AU - Chih-Yu Chao
PY - 2026
DA - 2026/10/15
JO - Molecular Medicine Reports
DO - 10.3892/mmr.2026.14043
UR - https://doi.org/10.3892/mmr.2026.14043
AB - Non-small cell lung cancer (NSCLC), as the predominant subtype of lung cancer, presents a considerable clinical challenge due to its high rates of recurrence and the significant adverse effects associated with conventional therapeutic modalities. In response to these challenges, the present study has explored the combined anticancer effects of epigallocatechin gallate (EGCG) together with thermal cycling-stimulation (TCS). The findings obtained demonstrated that the combination of EGCG and TCS led to a synergistic decrease in the viability of A549 and NCI-H460 NSCLC cells, whereas IMR-90 normal lung fibroblasts exhibited minimal cytotoxic effects. Further investigations revealed that EGCG could mitigate the TCS-induced upregulation of the heat shock proteins (HSPs) HSP70 and HSP105, whereas the expression levels of proteasome subunits were concurrently decreased. These alterations were accompanied by the disruption of proteostasis, and also by the activation of endoplasmic reticulum (ER) stress-associated pathways. Furthermore, pharmacological inhibition studies suggested a mutual interplay between inositol 1,4,5-trisphosphate receptor-mediated ER Ca2+ release and an excessive production of reactive oxygen species, ultimately causing the cells to undergo mitochondrial apoptosis. In summary, the present study has shown that the combined treatment of EGCG and TCS reduces the required dosage of EGCG, while also attenuating TCS-induced heat shock responses. Consequently, the present study offers a novel and promising in vitro proof-of-concept strategy for treating NSCLC.
SN - 1791-2997
SN - 1791-3004
ER -