Autophagy is the dominant type of programmed cell death in breast cancer MCF-7 cells exposed to AGS 115 and EFDAC, new sesquiterpene analogs of paclitaxel

Magdalena Górka, Włodzimierz M. Daniewski, Barbara Gajkowska, Elzbieta Łusakowska, Michał M. Godlewski, Tomasz Motyl*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    41 Citations (Scopus)

    Abstract

    The molecular mechanism of cell death induced by AGS 115 and EFDAC, sesquiterpene analogs of paclitaxel, was investigated in human breast cancer MCF-7 cells. The study was carried out using laser scanning cytometry, homeostatic confocal microscopy, atomic force microscopy and electron microscopy. AGS 115 and EFDAC exhibited a microtubule-stabilizing effect as confirmed by a significant increase in α-tubulin aggregation. Both paclitaxel analogs also induced death in MCF-7 cells. Evaluation of biochemical and morphological features suggested that the major form of programmed cell death induced by AGS 115 and EFDAC was autophagy. This was confirmed by MAP I LC3 expression and the ultrastructural pattern revealed by electron microscopy. Surface images of cells undergoing autophagy showed that, unlike during apoptosis, the dimensions remained unchanged, but the surface of the cell was deformed. The occurrence of apoptosis was confirmed by the efflux of Smac/DIABLO from mitochondria, caspase-7 activation and DNA loss, and did not exceed 9.7%. Therefore, AGS 115 and EFDAC appear to be promising candidates for further investigation in anti-cancer therapy.

    Original languageEnglish
    Pages (from-to)777-788
    Number of pages12
    JournalAnti-Cancer Drugs
    Volume16
    Issue number7
    DOIs
    Publication statusPublished - Aug 2005

    Keywords

    • AGS 115
    • Apoptosis
    • Autophagy
    • EFDAC
    • Sesquiterpene

    Fingerprint

    Dive into the research topics of 'Autophagy is the dominant type of programmed cell death in breast cancer MCF-7 cells exposed to AGS 115 and EFDAC, new sesquiterpene analogs of paclitaxel'. Together they form a unique fingerprint.

    Cite this