2. Academic Validation
  3. Anticancer activity of a novel small molecule tubulin inhibitor STK899704

Anticancer activity of a novel small molecule tubulin inhibitor STK899704

  • PLoS One. 2017 Mar 15;12(3):e0173311. doi: 10.1371/journal.pone.0173311.
Krisada Sakchaisri 1 2,  Sun-Ok Kim 1,  Joonsung Hwang 1,  Nak Kyun Soung 1,  Kyung Ho Lee 1,  Tae Woong Choi 1,  Yongjun Lee 1,  Chan-Mi Park 1,  Naraganahalli R Thimmegowda 1,  Phil Young Lee 1,  Bettaswamigowda Shwetha 1,  Ganipisetti Srinivasrao 1,  Thi Thu Huong Pham 1 3,  Jae-Hyuk Jang 1,  Hye-Won Yum 4,  Young-Joon Surh 4,  Kyung S Lee 5,  Hwangseo Park 6,  Seung Jun Kim 7,  Yong Tae Kwon 8,  Jong Seog Ahn 1,  Bo Yeon Kim 1
Affiliations

Affiliations

  • 1 Anticancer Agents Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongwon, Korea.
  • 2 Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
  • 3 The Key Laboratory of Enzyme & Protein Technology (KLEPT), VNU University of Science, Vietnam National University, Hanoi, Vietnam.
  • 4 College of Pharmacy, Seoul National University, Seoul, Korea.
  • 5 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
  • 6 Department of Bioscience and Biotechnology, Sejong University, Seoul, Korea.
  • 7 Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
  • 8 Department of Biomedical Sciences and Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, Korea.
PMID: 28296906 DOI: 10.1371/journal.pone.0173311
Abstract

We have identified the small molecule STK899704 as a structurally novel tubulin inhibitor. STK899704 suppressed the proliferation of Cancer cell lines from various origins with IC50 values ranging from 0.2 to 1.0 μM. STK899704 prevented the polymerization of purified tubulin in vitro and also depolymerized microtubule in cultured cells leading to mitotic arrest, associated with increased Cdc25C phosphorylation and the accumulation of both cyclin B1 and polo-like kinase 1 (PLK1), and Apoptosis. Unlike many Anticancer drugs such as Taxol and doxorubicin, STK899704 effectively displayed antiproliferative activity against multidrug-resistant Cancer cell lines. The proposed binding mode of STK899704 is at the interface between αβ-tubulin heterodimer overlapping with the colchicine-binding site. Our in vivo carcinogenesis model further showed that STK 899704 is potent in both the prevention and regression of tumors, remarkably reducing the number and volume of skin tumor by STK899704 treatment. Moreover, it was significant to note that the efficacy of STK899704 was surprisingly comparable to 5-fluorouracil, a widely used Anticancer therapeutic. Thus, our results demonstrate the potential of STK899704 to be developed as an Anticancer chemotherapeutic and an alternative candidate for existing therapies.

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