English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Survivin is a dual function protein. It inhibits the apoptosis of cells by inhibiting caspases, and also promotes cell growth by stabilizing microtubules during mitosis. Over-expression of survivin has been demonstrated to induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA damaging agent) and paclitaxel (microtubule stabilizer) in cancers. However, survivin-induced resistance to microtubule de-stabilizers such as  Vinca  alkaloids and Combretastatin A-4 (CA-4)-related compounds were seldom demonstrated in the past. Furthermore, the question remains as to whether survivin plays a dominant role in processing cytokinesis or inhibiting caspases activity in cells treated with anti-mitotic compounds. The purpose of this study is to evaluate the effect of survivin on the resistance and susceptibility of human cancer cells to microtubule de-stabilizer-induced cell death.    Results  BPR0L075 is a CA-4 analog that induces microtubule de-polymerization and subsequent caspase-dependent apoptosis. To study the relationship between the expression of survivin and the resistance to microtubule de-stabilizers, a KB-derived BPR0L075-resistant cancer cell line, KB- L30 , was generated for this study. Here, we found that survivin was over-expressed in the KB- L30  cells. Down-regulation of survivin by siRNA induced hyper-sensitivity to BPR0L075 in KB cells and partially re-stored sensitivity to BPR0L075 in KB- L30  cells. Western blot analysis revealed that down-regulation of survivin induced microtubule de-stabilization in both KB and KB- L30  cells. However, the same treatment did not enhance the down-stream caspase-3/-7 activities in BPR0L075-treated KB cells. Translocation of a caspase-independent apoptosis-related molecule, apoptosis-inducing factor (AIF), from cytoplasm to the nucleus was observed in survivin-targeted KB cells under BPR0L075 treatment.    Conclusion  In this study, survivin plays an important role in the stability of microtubules, but not with caspases inhibition. Over-expression of survivin counteracts the therapeutic effect of microtubule de-stabilizer BPR0L075 probably by stabilizing tubulin polymers, instead of the inhibition of caspase activity in cancer cells. Besides microtubule-related caspase-dependent cell death, caspase-independent mitotic cell death could be initiated in survivin/BPR0L075 combination treatments. We suggest that combining microtubule de-stabilizers with a survivin inhibitor may attribute to a better clinical outcome than the use of anti-mitotic monotherapy in clinical situations.

Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers