title: Doxycycline induces apoptosis by way of caspase-3 activation with inhibition of matrix metalloproteinase in human T-lymphoblastic leukemia CCRF-CEM cells.
abstract: Evidence for nonantibiotic activity displayed by tetracycline has been extensively reported in the field of antiinflammation. Here, we report a growth-inhibitory effect of doxycycline on CCRF-CEM, a T-lymphoblastic human leukemic cell line. Cells were incubated with doxycycline at concentrations ranging from zero to 50 micromol/L. We examined the hypothesis that induction of apoptosis is one of the mechanisms by which doxycycline inhibits CCRF-CEM proliferation. Caspase-3 activity of cells grown in the presence of 10 micromol/L and 50 micromol/L doxycycline increased dose-dependently after 24 hours in culture. The demonstration that doxycycline induces APO 2.7 expression in CCRF-CEM cells in vitro also supports its capacity for induction of apoptosis. The level of matrix metalloproteinase-2 was significantly lower in the medium cultured with 50 micromol/L doxycycline than the control. These phenomena suggest that this well-tolerated oral agent has the potential to be of value in antileukemic therapy.
authors.affiliation: Division of Transfusion Medicine, First Department of Internal Medicine, Fukui Medical University, Matsuoka, Fukui, Japan. hiwasaki@fmsrsa.fukui-med.ac.jp
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mitsuke
authors.forename: Adel
authors.initials: A
authors.lastname: Badran
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikegaya
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D015458:Leukemia, T-Cell; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000900:Anti-Bacterial Agents; D061965:Matrix Metalloproteinase Inhibitors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline