Peloruside A inhibits growth of human lung and breast tumor xenografts in an Athymic nu/nu mouse model

Colin J. Meyer, Melissa Krauth, Michael J. Wick, Jerry W. Shay, Ginelle Gellert, Jef K. De Brabander, Peter T. Northcote, John H. Miller

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Peloruside A is a microtubule-stabilizing agent isolated from a New Zealand marine sponge. Peloruside prevents growth of a panel of cancer cell lines at low nanomolar concentrations, including cell lines that are resistant to paclitaxel. Three xenograft studies in athymic nu/nu mice were performed to assess the efficacy of peloruside compared with standard anticancer agents such as paclitaxel, docetaxel, and doxorubicin. The first study examined the effect of 5 and 10 mg/kg peloruside (QDx5) on the growth of H460 non-small cell lung cancer xenografts. Peloruside caused tumor growth inhibition (%TGI) of 84% and 95%, respectively, whereas standard treatments with paclitaxel (8 mg/kg, QDx5) and docetaxel (6.3 mg/kg, Q2Dx3) were much less effective (%TGI of 50% and 18%, respectively). In a second xenograft study using A549 lung cancer cells and varied schedules of dosing, activity of peloruside was again superior compared with the taxanes with inhibitions ranging from 51% to 74%, compared with 44% and 50% for the two taxanes. A third xenograft study in a P-glycoprotein-overexpressing NCI/ADR-RES breast tumor model showed that peloruside was better tolerated than either doxorubicin or paclitaxel. We conclude that peloruside is highly effective in preventing the growth of lung and P-glycoprotein-overexpressing breast tumors in vivo and that further therapeutic development is warranted.

Original languageEnglish (US)
Pages (from-to)1816-1823
Number of pages8
JournalMolecular Cancer Therapeutics
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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