دورية أكاديمية
أعرض في EDS

Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells.

التفاصيل البيبلوغرافية
العنوان: Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells.
المؤلفون: Jaunky DB; Department of Biology, Concordia University, Montreal, QC, Canada., Larocque K; Department of Biology, Concordia University, Montreal, QC, Canada., Husser MC; Department of Biology, Concordia University, Montreal, QC, Canada., Liu JT; Department of Chemistry and Biochemistry, Concordia University, Montreal, QC, Canada., Forgione P; Department of Chemistry and Biochemistry, Concordia University, Montreal, QC, Canada., Piekny A; Department of Biology, Concordia University, Montreal, QC, Canada. alisa.piekny@concordia.ca.
المصدر: Scientific reports [Sci Rep] 2021 Dec 08; Vol. 11 (1), pp. 23665. Date of Electronic Publication: 2021 Dec 08.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Isoquinolines/*pharmacology , Microtubules/*drug effects , Mitosis/*drug effects , Spindle Apparatus/*drug effects , Spindle Poles/*drug effects, Cell Line, Tumor ; Cells, Cultured ; Colchicine/pharmacology ; Humans ; Isoquinolines/chemistry ; Microtubules/metabolism ; Thiophenes/chemistry
مستخلص: We reveal the effects of a new microtubule-destabilizing compound in human cells. C75 has a core thienoisoquinoline scaffold with several functional groups amenable to modification. Previously we found that sub micromolar concentrations of C75 caused cytotoxicity. We also found that C75 inhibited microtubule polymerization and competed with colchicine for tubulin-binding in vitro. However, here we found that the two compounds synergized suggesting differences in their mechanism of action. Indeed, live imaging revealed that C75 causes different spindle phenotypes compared to colchicine. Spindles remained bipolar and collapsed after colchicine treatment, while C75 caused bipolar spindles to become multipolar. Importantly, microtubules rapidly disappeared after C75-treatment, but then grew back unevenly and from multiple poles. The C75 spindle phenotype is reminiscent of phenotypes caused by depletion of ch-TOG, a microtubule polymerase, suggesting that C75 blocks microtubule polymerization in metaphase cells. C75 also caused an increase in the number of spindle poles in paclitaxel-treated cells, and combining low amounts of C75 and paclitaxel caused greater regression of multicellular tumour spheroids compared to each compound on their own. These findings warrant further exploration of C75's anti-cancer potential.
(© 2021. The Author(s).)
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المشرفين على المادة: 0 (Isoquinolines)
0 (Thiophenes)
JGX76Y85M6 (isoquinoline)
SML2Y3J35T (Colchicine)
تواريخ الأحداث: Date Created: 20211209 Date Completed: 20220128 Latest Revision: 20220128
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8655040
DOI: 10.1038/s41598-021-03076-3
PMID: 34880347
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-021-03076-3