An article published this year in “Clinical Cancer Research” using one of our products, “MitoStep + FITC Apoptosis Detection Kit”, by our customers from the Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain and the Hematology Department, University Hospital of Salamanca, SpainU, in the analysis of how Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myeloma. Congrats and Thanks.
Summay:
Amiloride-induced apoptosis was observed in a broad panel of MM cell
lines and in a xenograft mouse model. Moreover, amiloride also had a
synergistic effect when combined with dexamethasone, melphalan, lenalidomide
and pomalidomide. RNA-Seq experiments showed that amiloride not only
significantly altered the level of transcript isoforms and alternative splicing
events, but also deregulated the spliceosomal machinery. Additionally,
disruption of the splicing machinery in immunofluorescence studies was
associated with the inhibition of myeloma cell viability after amiloride
exposure. Although amiloride was able to induce apoptosis in myeloma cells
lacking p53 expression, activation of p53 signaling was observed in wild-type
and mutated TP53 cells after amiloride exposure. On the other hand, we did not
find a significant systemic toxicity in mice treated with amiloride.
Figure. Amiloride induces apoptosis, activates caspases and deregulates
mitochondrial potential in MM cell lines. H929, JJN3 and KMS12-BM cells were treated
with increasing concentrations of amiloride for 24 h. (A) The induction of apoptosis was
Research.
Downloaded from clincancerres.aacrjournals.org on August 9, 2017. © 2017 American Association for Cancer
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
Author Manuscript Published OnlineFirst on August 8, 2017; DOI: 10.1158/1078-0432.CCR-17-0678
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analyzed by flow cytometry after annexin-V/PI staining. (B) Mitochondrial membrane
depolarization was examined by flow cytometry after DilC1(5) staining. (C) The activity of
caspase 8, caspase 9 and caspase 3/7 was analyzed by luminescent caspase assays.
Results are expressed as the mean ± SD of three independent experiments. Statistically
significant differences between untreated and treated cell lines are represented as **p <
0.01 and *p < 0.05 (Student's t-test).
Reference:
Product link:
MitoStep + FITC
Apoptosis Detection Kit
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