Acquired resistance to peloruside A and laulimalide is associated with downregulation of vimentin in human ovarian carcinoma cells.

Pharmaceutical Research
Arun KanakkantharaJohn H Miller

Abstract

Acquired β-tubulin alterations in human ovarian carcinoma 1A9 cells were previously shown to confer resistance to the microtubule stabilizing agents peloruside A (PLA) and laulimalide (LAU). We examined the proteome of resistant cells to see what other protein changes occurred as a result of the acquired drug resistance. Two-dimensional differential in-gel electrophoresis was performed to explore differentially expressed proteins in the resistant 1A9-R1 (R1) and 1A9-L4 (L4) cells. The proteins on the gels were identified by MALDI-TOF MS, and altered protein abundance was confirmed by Western blotting and immunocytochemistry. Vimentin expression was restored in vimentin-deficient L4 cells by transfecting a full-length human vimentin cDNA, and sensitivity to PLA and LAU were tested using an MTT cell proliferation assay. Proteomic analysis identified several proteins that were significantly altered in the resistant cells relative to the parental 1A9 cells. Using Western blotting and immunocytochemistry, a decreased vimentin abundance in the L4 cells was validated. Vimentin levels were unchanged in PLA-resistant R1 cells and paclitaxel/epothilone-resistant derivatives of 1A9 cells. Vimentin cDNA transfection into L4 cells partially...Continue Reading

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Citations

Apr 24, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wamtinga Richard SawadogoMarc Diederich
Oct 14, 2017·Marine Drugs·Cinzia CalcabriniCarmela Fimognari
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Aug 1, 2020·Diagnostics·Isabel J Dionísio de SousaPaula Soares
Dec 30, 2020·Marine Drugs·Conxita Avila, Carlos Angulo-Preckler

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