Lauryl gallate induces apoptosis via p38-MAPK phosphorylation and autophagy in chemoresistant human lung cancer cells.

Human lung cancer has taken many lives and chemoresistance generally occurs in patients and reduces patients' survival. Docetaxel (DOC) and vincristine (VCR) have been widely used in cancer chemotherapy but their efficacy is restricted by P-glycoprotein (P-gp) overexpression. Lauryl gallate (LG) is a plant-derived small molecule which acts as antioxidant in normal cells. Surprisingly, LG also has been shown to control several types of cancer cells and induce apoptosis by way of induction of reactive oxygen species (ROS). To further clarify the anti-lung cancer activity of LG, we evaluated the cytotoxicity of LG using a previously established human A549/DOC resistant subline that has high P-gp expression and a A549/VCR resistant subline to determine their LG sensitivity by MTT assay. The apoptosis and autophagy levels were examined by protein analysis and flow cytometry. Interference of p38-MAPK and ATG5 expression by siRNAs was performed to measure the involvement of these two proteins in apoptosis and autophagy. We found that LG exerts higher cytotoxicity to the target cells when compared with tannic acid (TA) and octyl gallate (OG). Furthermore, LG not only induces apoptosis, it also enhances autophagy in both chemoresistant A549 sublines. When p38-MAPK was knocked down, the apoptosis level was reduced but autophagy was not. Knockdown of ATG5 resulted in significant apoptosis reduction in VCR-resistant A549 cells but less effect was found in DOC-resistant A549 cells. In sum, our data suggested that LG promotes p38-MAPK phosphorylation and induces apoptosis in chemoresistant A549 cells independently with P-gp expression. LG also enhances autophagy-regulated cell death in chemoresistant lung cancer cells.