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CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers

In the past, several microtubule targeting agents (MTAs) have been developed into successful anticancer drugs. However, the usage of these drugs has been limited by the acquisition of drug resistance in many cancers. Therefore, there is a constant demand for the development of new therapeutic drugs....

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Autores principales: Han, Ho Jin, Park, Chanmi, Hwang, Joonsung, N.R., Thimmegowda, Kim, Sun-Ok, Han, Junyeol, Woo, Minsik, B, Shwetha, Ryoo, In-Ja, Lee, Kyung Ho, Cha-Molstad, Hyunjoo, Kwon, Yong Tae, Kim, Bo Yeon, Soung, Nak-Kyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370279/
https://www.ncbi.nlm.nih.gov/pubmed/32645923
http://dx.doi.org/10.3390/ijms21134800
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author Han, Ho Jin
Park, Chanmi
Hwang, Joonsung
N.R., Thimmegowda
Kim, Sun-Ok
Han, Junyeol
Woo, Minsik
B, Shwetha
Ryoo, In-Ja
Lee, Kyung Ho
Cha-Molstad, Hyunjoo
Kwon, Yong Tae
Kim, Bo Yeon
Soung, Nak-Kyun
author_facet Han, Ho Jin
Park, Chanmi
Hwang, Joonsung
N.R., Thimmegowda
Kim, Sun-Ok
Han, Junyeol
Woo, Minsik
B, Shwetha
Ryoo, In-Ja
Lee, Kyung Ho
Cha-Molstad, Hyunjoo
Kwon, Yong Tae
Kim, Bo Yeon
Soung, Nak-Kyun
author_sort Han, Ho Jin
collection PubMed
description In the past, several microtubule targeting agents (MTAs) have been developed into successful anticancer drugs. However, the usage of these drugs has been limited by the acquisition of drug resistance in many cancers. Therefore, there is a constant demand for the development of new therapeutic drugs. Here we report the discovery of 5-5 (3-cchlorophenyl)-N-(3-pyridinyl)-2-furamide (CPPF), a novel microtubule targeting anticancer agent. Using both 2D and 3D culture systems, we showed that CPPF was able to suppress the proliferation of diverse cancer cell lines. In addition, CPPF was able to inhibit the growth of multidrug-resistant cell lines that are resistant to other MTAs, such as paclitaxel and colchicine. Our results showed that CPPF inhibited growth by depolymerizing microtubules leading to mitotic arrest and apoptosis. We also confirmed CPPF anticancer effects in vivo using both a mouse xenograft and a two-step skin cancer mouse model. Using established zebrafish models, we showed that CPPF has low toxicity in vivo. Overall, our study proves that CPPF has the potential to become a successful anticancer chemotherapeutic drug.
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spelling pubmed-73702792020-08-07 CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers Han, Ho Jin Park, Chanmi Hwang, Joonsung N.R., Thimmegowda Kim, Sun-Ok Han, Junyeol Woo, Minsik B, Shwetha Ryoo, In-Ja Lee, Kyung Ho Cha-Molstad, Hyunjoo Kwon, Yong Tae Kim, Bo Yeon Soung, Nak-Kyun Int J Mol Sci Article In the past, several microtubule targeting agents (MTAs) have been developed into successful anticancer drugs. However, the usage of these drugs has been limited by the acquisition of drug resistance in many cancers. Therefore, there is a constant demand for the development of new therapeutic drugs. Here we report the discovery of 5-5 (3-cchlorophenyl)-N-(3-pyridinyl)-2-furamide (CPPF), a novel microtubule targeting anticancer agent. Using both 2D and 3D culture systems, we showed that CPPF was able to suppress the proliferation of diverse cancer cell lines. In addition, CPPF was able to inhibit the growth of multidrug-resistant cell lines that are resistant to other MTAs, such as paclitaxel and colchicine. Our results showed that CPPF inhibited growth by depolymerizing microtubules leading to mitotic arrest and apoptosis. We also confirmed CPPF anticancer effects in vivo using both a mouse xenograft and a two-step skin cancer mouse model. Using established zebrafish models, we showed that CPPF has low toxicity in vivo. Overall, our study proves that CPPF has the potential to become a successful anticancer chemotherapeutic drug. MDPI 2020-07-07 /pmc/articles/PMC7370279/ /pubmed/32645923 http://dx.doi.org/10.3390/ijms21134800 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Ho Jin
Park, Chanmi
Hwang, Joonsung
N.R., Thimmegowda
Kim, Sun-Ok
Han, Junyeol
Woo, Minsik
B, Shwetha
Ryoo, In-Ja
Lee, Kyung Ho
Cha-Molstad, Hyunjoo
Kwon, Yong Tae
Kim, Bo Yeon
Soung, Nak-Kyun
CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers
title CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers
title_full CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers
title_fullStr CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers
title_full_unstemmed CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers
title_short CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers
title_sort cppf, a novel microtubule targeting anticancer agent, inhibits the growth of a wide variety of cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370279/
https://www.ncbi.nlm.nih.gov/pubmed/32645923
http://dx.doi.org/10.3390/ijms21134800
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