Inhibition of mesothelioma cell growth in vitro by doxycycline

Our plain-English summary of Inhibition of mesothelioma cell growth in vitro by doxycycline, by J.B. Rubins, D. Charboneau, M.D. Alter, et al (The Journal of Laboratory and Clinical Medicine, 2001).

The study

• Authors: J.B. Rubins, D. Charboneau, M.D. Alter, P.B. Bitterman, R.A. Kratzke
• Journal: The Journal of Laboratory and Clinical Medicine
• Published: 2001;138(2):101-6
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

In this laboratory study, the authors tested whether the antibiotic doxycycline slows the growth of human malignant mesothelioma cells in culture. Asbestos exposure and patients were not studied. Eight mesothelioma cell lines were treated, with normal human lung fibroblasts for comparison. The authors described 5 to 10 µg/mL as within the range reached in blood with oral doses of 200 mg per day. After 72 hours, 10 µg/mL cut mesothelioma cell numbers by 25% to 80%, depending on the line, and 20 µg/mL cut every line by at least 50%. Fibroblasts needed 50 to 75 µg/mL for a 50% reduction. In most lines, cell numbers did not fall below starting levels. The authors took this to suggest mainly growth suppression rather than cell killing; three sensitive lines were exceptions. Effects on the mitochondrial enzyme cytochrome c oxidase ranged from 85% inhibition to slight increases and did not appear to track growth sensitivity. Doxycycline did not appreciably change how much gelatinase A activity the cells released, but it directly inhibited the enzyme's activity. The authors concluded that doxycycline warrants further study as a potential add-on therapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell culture experiment
• Who was studied: Eight human malignant mesothelioma cell lines: some derived at the National Cancer Institute–Navy Medical Oncology Branch, plus lines bought from the American Type Culture Collection (CRL-5820, CRL-5915, CRL-2081). Normal human lung fibroblasts (ATCC CCL 210) were the control. The authors were based in Minneapolis, Minnesota.
• Exposure: Doxycycline added to the culture medium. The authors described 5 to 10 µg/mL as in the range reached in serum after oral doses of 200 mg per day. 20 µg/mL was also tested on mesothelioma cells, and fibroblasts needed 50 to 75 µg/mL for 50% inhibition. The study did not examine asbestos or any fiber exposure.
• Main results:
  • At 10 µg/mL for 72 hours, mesothelioma cell numbers fell by 25% to 80% depending on the cell line. The table gives growth inhibition from 79.4 ± 3.6% (line 2373) down to 25.2 ± 9.8% (line 513).
  • At 20 µg/mL for 72 hours, every mesothelioma cell line showed at least a 50% reduction in cell number.
  • Normal human fibroblasts were more resistant and needed 50 to 75 µg/mL for 50% growth inhibition. These data were not shown in the article.
  • In most mesothelioma lines treated for up to 72 hours, cell numbers did not fall below starting numbers. The authors took this to suggest that, for most lines, these concentrations were predominantly cytostatic (growth-suppressing) rather than cytotoxic (cell-killing). The exceptions were the highly sensitive lines 2595, 5820 and 2373.
  • Effects of 10 µg/mL doxycycline on mitochondrial cytochrome c oxidase activity varied by cell line, from 85% inhibition to slight increases. The authors found no appreciable overall correlation between this effect and growth inhibition across the eight lines.
  • Treating the cells with doxycycline did not appreciably change how much gelatinase A activity they released into the culture medium.
  • When the separated gelatinase A was incubated directly with 10 µg/mL doxycycline, its activity was significantly inhibited for all mesothelioma cell lines.
• The authors' conclusion: The authors concluded that doxycycline can substantially inhibit mesothelioma cell growth in vitro at concentrations achievable in serum with typical oral doses. They concluded that, together with earlier reports, their data support further investigation of doxycycline as a potential adjunctive therapy for mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Chemotherapy, Fibroblast, Adjuvant Therapy.

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