title: Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-κB inactivation.
abstract: 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 G0/G1 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 Bcl-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 μM) than on K562 cells (IC50 33 μM). 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-κB. In conclusion, GA induced apoptosis in K562 cells involves death receptor and mitochondrial-mediated pathways by inhibiting BCR/ABL kinase, NF-κB activity and COX-2.
authors.affiliation: Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: T
authors.initials: T
authors.lastname: Chandramohan Reddy
authors.forename: D
authors.initials: D
authors.lastname: Bharat Reddy
authors.forename: A
authors.initials: A
authors.lastname: Aparna
authors.forename: Kalle M
authors.initials: KM
authors.lastname: Arunasree
authors.forename: Geetika
authors.initials: G
authors.lastname: Gupta
authors.forename: Chandrani
authors.initials: C
authors.lastname: Achari
authors.forename: G V
authors.initials: GV
authors.lastname: Reddy
authors.forename: V
authors.initials: V
authors.lastname: Lakshmipathi
authors.forename: A
authors.initials: A
authors.lastname: Subramanyam
authors.forename: P
authors.initials: P
authors.lastname: Reddanna
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D005707:Gallic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D000068877:Imatinib Mesylate; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016328:NF-kappa B; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D005707:Gallic Acid; D000068877:Imatinib Mesylate; D051546:Cyclooxygenase 2; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl