Effects of okadaic acid and hematein on human lung adenocarcinoma A549 cells and responses of mitochondria and endoplasmic reticulum apoptosis pathways

BACKGROUND: Okadaic acid (OA) and hematein are both able to inhibit the proliferation of human lung adenocarcinoma A549 cells. However, it is largely unknown about their combined effects on proliferation and apoptosis of A549 cells. METHODS: The combined effects of the two drugs on proliferation of A549 cells and the responses of mitochondria and endoplasmic reticulum (ER) apoptosis pathways were investigated. RESULTS: MTT assay showed that both OA and hematein significantly inhibited proliferation of A549 cells, and the combined drugs could further increase the inhibition ratio with lower dosages. Inverted phase contrast microscope and scanning electron microscope (SEM) analysis indicated that the combined drugs aggravated the appearance of apoptotic bodies and damaged cells. Compared to the single drug treated groups, reactive oxygen species (ROS) contents were significantly higher in the groups treated by the combined drugs, and mitochondrial membrane potential was significant lower. Western blot indicated that pro-apoptotic Bax that involved in mitochondrial apoptosis pathway increased, the anti-apoptotic protein Bcl-2 decreased, and the ER apoptosis-related proteins CHOP, Calpain2, JNK1 and IRE1 increased. CONCLUSIONS: This work demonstrates that OA combined hematein can more effectively inhibit proliferation of A549 cells, and induce apoptosis of A549 cells via mitochondria and ER dependent pathways.