Open AccessAnticancer activity of a novel small molecule tubulin inhibitor STK899704
Author(s) -
Krisada Sakchaisri,
Sun Ok Kim,
Joonsung Hwang,
Nak-Kyun Soung,
Kyung Ho Lee,
Thomas Y. Choi,
Yong-Jun Lee,
Chan Mi Park,
N. R. Thimmegowda,
Phil Young Lee,
B. Shwetha,
Ganipisetti Srinivasrao,
Thi Thu Huong Pham,
Jae Hyuk Jang,
Hye Won Yum,
Young Joon Surh,
Kyung S. Lee,
Hwangseo Park,
Seung Jun Kim,
Yong Tae Kwon,
Jong Seog Ahn,
Bo Yeon Kim
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0173311
Subject(s) - tubulin , doxorubicin , microtubule , in vivo , plk1 , cancer research , cyclin b1 , biology , kinase , mitosis , antimitotic agent , apoptosis , colchicine , cancer cell , chemistry , cyclin dependent kinase 1 , cell cycle , cancer , biochemistry , microbiology and biotechnology , chemotherapy , genetics
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 IC 50 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.