A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells

Stehn, Justine R.; Haass, Nikolas K.; Allanson, Munif; Fath, Thomas; Hill, Timothy A.; McCluskey, Adam; Schevzov, Galina; Palmer, Stephen J.; Hardeman, Edna C.; Winlaw, David; Reeve, Vivienne E.; Dixon, Ian; Bonello, Teresa; Weninger, Wolfgang; Cripe, Timothy P.; Gunning, Peter W.; Desouza, Melissa; Kottyan, Gregg; Treutlein, Herbert; Zeng, Jun; Nascimento, Paula R. B. B.; Sequeira, Vanessa B.; Butler, Tanya L.

Title: A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells
Creator: Stehn, Justine R.; Haass, Nikolas K.; Allanson, Munif; Fath, Thomas; Hill, Timothy A.; McCluskey, Adam; Schevzov, Galina; Palmer, Stephen J.; Hardeman, Edna C.; Winlaw, David; Reeve, Vivienne E.; Dixon, Ian; Bonello, Teresa; Weninger, Wolfgang; Cripe, Timothy P.; Gunning, Peter W.; Desouza, Melissa; Kottyan, Gregg; Treutlein, Herbert; Zeng, Jun; Nascimento, Paula R. B. B.; Sequeira, Vanessa B.; Butler, Tanya L.
Relation: NHMRC.1004188
Relation: Cancer Research Vol. 73, Issue 16, p. 5169-5182
Publisher Link: http://dx.doi.org/10.1158/0008-5472.CAN-12-4501
Publisher: American Association for Cancer Research
Resource Type: journal article
Date: 2013
Description: The actin cytoskeleton is a potentially vulnerable property of cancer cells, yet chemotherapeutic targeting attempts have been hampered by unacceptable toxicity. In this study, we have shown that it is possible to disrupt specific actin filament populations by targeting isoforms of tropomyosin, a core component of actin filaments, that are selectively upregulated in cancers. A novel class of anti-tropomyosin compounds has been developed that preferentially disrupts the actin cytoskeleton of tumor cells, impairing both tumor cell motility and viability. Our lead compound, TR100, is effective in vitro and in vivo in reducing tumor cell growth in neuroblastoma and melanoma models. Importantly, TR100 shows no adverse impact on cardiac structure and function, which is the major side effect of current anti-actin drugs. This proof-of-principle study shows that it is possible to target specific actin filament populations fundamental to tumor cell viability based on their tropomyosin isoform composition. This improvement in specificity provides a pathway to the development of a novel class of anti-actin compounds for the potential treatment of a wide variety of cancers.
Subject: anticancer compounds; actin cytoskeleton; tumor cells
Identifier: http://hdl.handle.net/1959.13/1298316
Identifier: uon:19635
Identifier: ISSN:0008-5472
Language: eng
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