Influence of chemically modified tetracyclines on proliferation, invasion and migration properties of MDA-MB-468 human breast cancer cells.
Chemically modified tetracyclines (CMTs) are promising anti-cancer agents. In this study, we found that CMT-3 and CMT-8 showed dose-dependent cytotoxicities in MDA-MB-468 human breast cancer cells. Moreover, both CMT-3 and CMT-8 significantly inhibited in vitro cell migration and invasion at non-cytotoxic concentrations. Anti-invasion and migration potentials of the CMTs were associated with an increased expression of E-cadherin/catenins (alpha, beta and gamma-catenin) and tumor suppressor BRCA1. In addition, CMT-3 and CMT-8 abolished or reduced spontaneous and HGF/SF-induced cell invasion and migration in U-373 MG human glioblastoma cells. Our current finding is the first demonstration that CMT-3 and CMT-8 can activate the function of invasion suppressor molecules associated with the suppression of breast cancer cell invasion and migration. Thus, clinical application of CMTs may provide potential benefit for suppression of breast cancer growth, invasion and metastasis.
Department of Radiation Oncology, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
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Meng
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Xu
I D
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Goldberg
E M
EM
Rosen
R A
RA
Greenwald
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Fan
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D013754:Tetracyclines / Q000737:chemistry / Q000494:pharmacology*; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D013754:Tetracyclines; D015534:Trans-Activators; D051176:beta Catenin