title: Apoptotic cell death through inhibition of protein kinase CKII activity by 3,4-dihydroxybenzaldehyde purified from Xanthium strumarium.
abstract: The CKII inhibitory compound was purified from the fruit of Xanthium strumarium by organic solvent extraction and silica gel chromatography. The inhibitory compound was identified as 3,4-dihydroxybenzaldehyde by analysis with FT-IR, FAB-Mass, EI-Mass, (1)H-NMR and (13)C-NMR. 3,4-dihydroxybenzaldehyde inhibited the phosphotransferase activity of CKII with IC(50) of about 783 microM. Steady-state studies revealed that the inhibitor acts as a competitive inhibitor with respect to the substrate ATP. A value of 138.6 microM was obtained for the apparent K(i). Concentration of 300 microM 3,4-dihydroxybenzaldehyde caused 50% growth inhibition of human cancer cell U937. 3,4-dihydroxybenzaldehyde-induced cell death was characterised with the cleavage of poly(ADP-ribose) polymerase and procaspase-3. Furthermore, the inhibitor induced the fragmentation of DNA into multiples of 180 bp, indicating that it triggered apoptosis. This induction of apoptosis by 3,4-dihydroxybenzaldehyde was also confirmed by using flow cytometry analysis. Since CKII is involved in cell proliferation and oncogenesis, these results suggest that 3,4-dihydroxybenzaldehyde may function by inhibiting oncogenic disease, at least in part, through the inhibition of CKII activity.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: Bang Hyo
authors.initials: BH
authors.lastname: Lee
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Yoon
authors.forename: Yun-Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Kim
authors.forename: Byong Jo
authors.initials: BJ
authors.lastname: Moon
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001547:Benzaldehydes / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005638:Fruit / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D031210:Xanthium / Q000737:chemistry*
chemical_list: D001547:Benzaldehydes; D002396:Catechols; C005581:protocatechualdehyde; D047390:Casein Kinase II