Anti-leukemic effects of gallic acid on human leukemia K562 cells: Downregulation of COX-2, inhibition of BCR/ABL kinase and NF-κB inactivation

Gallic acid (GA) induces apoptosis in various cancer cell lines. In this study, we investigated the apoptotic activity induced by GA on chronic myeloid leukemia (CML) cell line-K562 and the underlying mechanism. GA reduced the viability of K562 cells in a dose and time dependent manner. GA led to G(0)/G(1) phase arrest in K562 cells by promoting p21 and p27 and inhibiting the levels of cyclin D and cyclin E. Further studies indicated apoptosis with impaired mitochondrial function as a result of deranged BcI-2/Bax ratio, leakage of cytochrome c and PARP cleavage along with DNA fragmentation and by up-regulating the expression of caspase-3. GA also activated the protein expressions of fatty acid synthase ligand and caspase-8. GA is more effective in imatinib resistant-K562 (IR-K562) cells (IC50 4 mu M) than on K562 cells (IC50 33 mu M). GA inhibited cyclooxygenase-2 (COX-2) in K562 as well as IR-K562 cells appears to be COX-2 involved in the suppression of growth. Interestingly, GA also inhibited BCR/ABL tyrosine kinase and NF-kappa B. In conclusion, GA induced apoptosis in K562 cells involves death receptor and mitochondrial-mediated pathways by inhibiting BCR/ABL kinase, NF-kappa B activity and COX-2. (C) 2012 Elsevier Ltd. All rights reserved.