当前位置： SCI文献检索 > BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS期刊下所有文献 > ALCAPs induce mitochondrial apoptosis and activate DNA damage response by generating ROS and inhibiting topoisomerase I enzyme activity in K562 leukemia cell line.

ALCAPs induce mitochondrial apoptosis and activate DNA damage response by generating ROS and inhibiting topoisomerase I enzyme activity in K562 leukemia cell line.

Abstract：

:Endemic Alkanna cappadocica was used to isolate novel antitumor molecules from Turkish landscapes in our previous studies. In this study, deoxyalkannin (ALCAP1), β,β-dimethylacrylalkannin (ALCAP2), acetylalkannin (ALCAP3), and alkannin (ALCAP4) as well as the novel isolated compounds 5-methoxydeoxyalkannin (ALCAP5), 8-methoxydeoxyalkannin (ALCAP6), 5-methoxyacetylalkannin (ALCAP7), 5-methoxy-β,β-dimethylacrylalkannin (ALCAP8) were characterized. The topoisomerase I (topo I) inhibitory activity of ALCAPs was investigated using in vitro plasmid relaxation assay and found that ALCAP2, 3, 4 and 7 were potent inhibitors at 2-6μM concentrations. Further, DNA damage response to ALCAP treatments was also studied by measuring the H2AX((S139)) and ATM((S1981)) phosphorylations. ALCAP2, 7 and 8 induced the DNA damage and apoptosis, consistently resulted in PARP cleavage at nanomolar concentrations in K562 leukemia cells. Moreover, when the free radical (ROS) generating capacity of the compounds was studied by 2',7'-dichlorofluorescein-diacetate assay using flow cytometry, we found that a known antioxidant N-acetyl-cysteine almost completely abrogated the H2AX((S139)) phosphorylations and the caspase 3 cleavage and activation. Thus, γH2AX((S139)) foci formation remained higher than the control, and an increase in CHK2((T68)) phosphorylation was observed by ALCAP2 and 7 treatments suggested that, these compounds can be potential therapeutics against tumor cell growth because of their unique DNA damaging abilities additional to enzyme inhibition similar to those of doxorubicin.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Bogurcu N,Sevimli-Gur C,Ozmen B,Bedir E,Korkmaz KS

doi

10.1016/j.bbrc.2011.05.078

subject

Has Abstract

pub_date

2011-06-17 00:00:00

pages

738-44

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(11)00845-X

journal_volume

409

pub_type

杂志文章

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