G2 arrest and apoptosis by 2-amino-N-quinoline-8-yl-benzenesulfonamide (QBS), a novel cytotoxic compound.
We screened a library of 11,000 small molecular weight chemicals, looking for compounds that affect cell viability. We have identified 2-amino-N-quinoline-8-yl-benzenesulfonamide (QBS) as a potent cytotoxic compound that induces cell cycle arrest and apoptosis. Treatment of Jurkat T cells with QBS increased the levels of cyclin B1 as well as phosphorylated-cdc2, which was accompanied by reduced activity of cdc2 kinase, suggesting that QBS may induce cell cycle arrest at G2 phase. Structural analogues of QBS also exhibited similar effects on cell cycle progression and cell viability. Long-term treatment with QBS resulted in DNA fragmentation, cytochrome C release, and PARP cleavage, and an increase in the number of subdiploidy cells, indicative of cellular apoptosis. Moreover, QBS-induced apoptosis was blocked by z-VAD-fmk, a pan-caspase inhibitor. These results suggest that QBS is a novel and potent compound that induces G2 arrest and subsequent apoptosis, implicating it as a putative candidate for chemotherapy.
Kim
Yun-Hee
YH
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31 Hyojadong, Nam-Gu, Pohang, Kyungbuk 790-784, Republic of Korea.
Shin
Kum-Joo
KJ
Lee
Taehoon G
TG
Kim
Euikyung
E
Lee
Myoung-Shik
MS
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D017209:Apoptosis / Q000187:drug effects*; D001554:Benzene / Q000737:chemistry / Q000633:toxicity*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D011419:Propidium; D011804:Quinolines / Q000737:chemistry / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D005456:Fluorescent Dyes; D011804:Quinolines; D011419:Propidium; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D016650:Fluorescein-5-isothiocyanate; D001554:Benzene