CYT997 causes apoptosis in human multiple myeloma

Katherine Monaghan, Tiffany Khong, Gregg Smith, Andrew Spencer

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Multiple Myeloma (MM) is an incurable malignancy of mature plasma cells. Microtubule targeting agents (MTAs) are an established class of drug that include many conventional and some novel compounds. MTAs function by inhibiting the polymerisation or depolymerisation of microtubules (MTs) within the cell, disrupting various important cellular functions. We have investigated pre-clinically the novel tubulin polymerisation inhibitor CYT997 for the potential treatment of MM. Here we demonstrate the promising anti-myeloma activity of CYT997 as evidenced by tubulin disruption, inhibition of growth and proliferation, cell cycle arrest and most importantly apoptosis of both human myeloma cell lines (HMCLs) and primary MM cells using nanomolar drug concentrations. CYT997 also synergises with bortezomib to produce more potent anti-MM activity. These in vitro observations were validated in vivo by the ability of CYT997 to significantly prolong survival in a murine model of aggressive systemic myelomatosis. These findings provide a basis for continuing pre-clinical and clinical investigations into the anti-MM effects of CYT997. A? Springer Science+Business Media, LLC 2009.
Original languageEnglish
Pages (from-to)232 - 238
Number of pages7
JournalInvestigational New Drugs
Volume29
Issue number2
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Monaghan, Katherine ; Khong, Tiffany ; Smith, Gregg ; Spencer, Andrew. / CYT997 causes apoptosis in human multiple myeloma. In: Investigational New Drugs. 2011 ; Vol. 29, No. 2. pp. 232 - 238.
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CYT997 causes apoptosis in human multiple myeloma. / Monaghan, Katherine; Khong, Tiffany; Smith, Gregg; Spencer, Andrew.

In: Investigational New Drugs, Vol. 29, No. 2, 2011, p. 232 - 238.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - CYT997 causes apoptosis in human multiple myeloma

AU - Monaghan, Katherine

AU - Khong, Tiffany

AU - Smith, Gregg

AU - Spencer, Andrew

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AB - Multiple Myeloma (MM) is an incurable malignancy of mature plasma cells. Microtubule targeting agents (MTAs) are an established class of drug that include many conventional and some novel compounds. MTAs function by inhibiting the polymerisation or depolymerisation of microtubules (MTs) within the cell, disrupting various important cellular functions. We have investigated pre-clinically the novel tubulin polymerisation inhibitor CYT997 for the potential treatment of MM. Here we demonstrate the promising anti-myeloma activity of CYT997 as evidenced by tubulin disruption, inhibition of growth and proliferation, cell cycle arrest and most importantly apoptosis of both human myeloma cell lines (HMCLs) and primary MM cells using nanomolar drug concentrations. CYT997 also synergises with bortezomib to produce more potent anti-MM activity. These in vitro observations were validated in vivo by the ability of CYT997 to significantly prolong survival in a murine model of aggressive systemic myelomatosis. These findings provide a basis for continuing pre-clinical and clinical investigations into the anti-MM effects of CYT997. A? Springer Science+Business Media, LLC 2009.

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