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Article

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

1
Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongju 28116, Korea
2
Department of Biomolecular Science, University of Science and Technology, Daejeon 34113, Korea
3
College of Pharmacy and Medical Research Center, Chungbuk National University, Osong, Cheongju 28160, Korea
4
Protein Metabolism Medical Research Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Korea
*
Authors to whom correspondence should be addressed.
These authors equally contributed to this work.
Current address: Government S.K.S.J.T Institute; Bangalore, Karnataka 560001, India.
§
Current address: Visvesvaraya Technological Institute, CPGS, Muddenahalli 562101, India.
Int. J. Mol. Sci. 2020, 21(13), 4800; https://doi.org/10.3390/ijms21134800
Received: 15 June 2020 / Revised: 4 July 2020 / Accepted: 6 July 2020 / Published: 7 July 2020
(This article belongs to the Section Molecular Pharmacology)
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. View Full-Text
Keywords: microtubule target agent; anticancer drug; skin cancer prevention/animal model; multidrug resistance; CPPF microtubule target agent; anticancer drug; skin cancer prevention/animal model; multidrug resistance; CPPF
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MDPI and ACS Style

Han, H.J.; Park, C.; Hwang, J.; N.R., T.; Kim, S.-O.; Han, J.; Woo, M.; B, S.; Ryoo, I.-J.; Lee, K.H.; Cha-Molstad, H.; Kwon, Y.T.; Kim, B.Y.; Soung, N.-K. CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers. Int. J. Mol. Sci. 2020, 21, 4800. https://doi.org/10.3390/ijms21134800

AMA Style

Han HJ, Park C, Hwang J, N.R. T, Kim S-O, Han J, Woo M, B S, Ryoo I-J, Lee KH, Cha-Molstad H, Kwon YT, Kim BY, Soung N-K. CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers. International Journal of Molecular Sciences. 2020; 21(13):4800. https://doi.org/10.3390/ijms21134800

Chicago/Turabian Style

Han, Ho Jin, Chanmi Park, Joonsung Hwang, Thimmegowda N.R., Sun-Ok Kim, Junyeol Han, Minsik Woo, Shwetha B, In-Ja Ryoo, Kyung Ho Lee, Hyunjoo Cha-Molstad, Yong Tae Kwon, Bo Yeon Kim, and Nak-Kyun Soung. 2020. "CPPF, A Novel Microtubule Targeting Anticancer Agent, Inhibits the Growth of a Wide Variety of Cancers" International Journal of Molecular Sciences 21, no. 13: 4800. https://doi.org/10.3390/ijms21134800

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