Inhibition of mesothelioma cell growth in vitro by doxycycline.
Malignant mesothelioma causes profound morbidity and nearly universal mortality that is often refractory to conventional treatment modalities of aggressive surgery, radiotherapy, or chemotherapy. Doxycycline, a commonly used antibiotic, has anti-tumor activity against several malignancies, but its anti-tumor effects on malignant mesothelioma have not been evaluated. We report here that concentrations of doxycycline achievable in serum with typical oral doses had cytostatic effects to varying extent on all eight of the mesothelioma cell lines studied but did not affect normal lung fibroblasts. Doxycycline inhibited the production of mitochondrial cytochrome c oxidase, especially in mesothelioma cells more sensitive to its cytostatic effects, and directly inhibited gelatinase A activity; both of these activities are putative mechanisms for the cytostatic activity of doxycycline in other tumor cells. Thus doxycycline may have a role as adjuvant therapy for malignant mesothelioma.
Rubins
J B
JB
Pulmonary Diseases and Oncology, Department of Medicine, Veterans Affairs Medical Center, Minneapolis, Minnesota, USA.
Charboneau
D
D
Alter
M D
MD
Bitterman
P B
PB
Kratzke
R A
RA
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008654:Mesothelioma; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000900:Anti-Bacterial Agents; D003576:Electron Transport Complex IV; D020778:Matrix Metalloproteinase 2; D004318:Doxycycline