Abstract
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.
Highlights
Chemotherapy has been a keystone of cancer treatment for many years
We screened small molecule library from the Korea Chemicals Banks looking for potential anticancer drugs using cell based antiproliferation assay and we identified of a novel microtubule targeting anticancer agent, 5-(3-chlorophenyl)-N-(3-pyridinyl)-2-furamide (CPPF)
We first tested the antiproliferative ability of CPPF on HeLa cells, a widely used cervical cancer cell line (Figure 1B)
Summary
Chemotherapy has been a keystone of cancer treatment for many years. Numerous therapeutic drugs have been developed [1]. Two successful chemotherapeutic drugs are vinblastine and paclitaxel. Vinblastine was isolated in 1958 and has been used to treat many cancers, including lymphoma, testicular cancer, breast cancer and choriocarcinoma [2] Paclitaxel was first isolated in 1971 and was approved for cancer treatment by the FDA in 1992. It has been broadly used to treat solid tumors such as breast cancer and metastatic non-small cell lung cancer [3]. Both vinblastine and paclitaxel are microtubule targeting agents (MTAs) [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
