Gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancers by accelerating EGFR turnover.
Gallic acid is a common botanic phenolic compound, which is present in plants and foods worldwide. Gallic acid is implicated in various biological processes such as cell growth and apoptosis. Indeed, gallic acid has been shown to induce apoptosis in many cancer types. However, the molecular mechanisms of gallic acid-induced apoptosis in cancer, particularly lung cancer, are still unclear. Here, we report that gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancer (NSCLC) cells, but not in EGFR-WT NSCLC cells. Treatment with gallic acid resulted in a significant reduction in proliferation and induction of apoptosis, only in EGFR-mutant NSCLC cells. Interestingly, treatment with gallic acid led to a robust decrease in EGFR levels, which is critical for NSCLC survival. Treatment with gallic acid had no significant effect on transcription, but induced EGFR turnover. Indeed, treatment with a proteasome inhibitor dramatically reversed gallic acid-induced EGFR downregulation. Moreover, treatment with gallic acid induced EGFR turnover leading to apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Thus, these studies suggest that gallic acid can induce apoptosis in EGFR-dependent lung cancers that are dependent on EGFR for growth and survival via acceleration of EGFR turnover.
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
Boas
B
Nam
Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea; Department of Convergence Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea.
Jin Kyung
JK
Rho
Department of Biomedical Sciences, Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Dong-Myung
DM
Shin
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, South Korea; Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea. Electronic address: jaekson@amc.seoul.kr.
Jaekyoung
J
Son
D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics*; D005707:Gallic Acid / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*
D005707:Gallic Acid; D066246:ErbB Receptors
EGFR; EGFR turnover; Gallic acid; Non-small cell lung cancer