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

Stehn, Justine R., Haass, Nikolas K., Bonello, Teresa, Desouza, Melissa, Kottyan, Gregg, Treutlein, Herbert, Zeng, Jun, Nascimento, Paula R. B. B., Sequeira, Vanessa B., Butler, Tanya L., Allanson, Munif, Fath, Thomas, Hill, Timothy A., McCluskey, Adam, Schevzov, Galina, Palmer, Stephen J., Hardeman, Edna C., Winlaw, David, Reeve, Vivienne E., Dixon, Ian, Weninger, Wolfgang, Cripe, Timothy P. and Gunning, Peter W. (2013) A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells. Cancer Research, 73 16: 5169-5182. doi:10.1158/0008-5472.CAN-12-4501


Author Stehn, Justine R.
Haass, Nikolas K.
Bonello, Teresa
Desouza, Melissa
Kottyan, Gregg
Treutlein, Herbert
Zeng, Jun
Nascimento, Paula R. B. B.
Sequeira, Vanessa B.
Butler, Tanya L.
Allanson, Munif
Fath, Thomas
Hill, Timothy A.
McCluskey, Adam
Schevzov, Galina
Palmer, Stephen J.
Hardeman, Edna C.
Winlaw, David
Reeve, Vivienne E.
Dixon, Ian
Weninger, Wolfgang
Cripe, Timothy P.
Gunning, Peter W.
Title A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
1538-7445
Publication date 2013-08-15
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-12-4501
Open Access Status
Volume 73
Issue 16
Start page 5169
End page 5182
Total pages 14
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2014
Language eng
Formatted abstract
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.
Keyword Distinct microfilament populations
Tropomyosin isoforms
Melanoma-cells
In-vitro
Cancer
Inhibitor
Growth
Expression
Apoptosis
Transformation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
UQ Diamantina Institute Publications
 
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