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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....
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7370279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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