Anticancer activity of a novel small molecule tubulin inhibitor STK899704

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 mu M. 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 multi-drug-resistant cancer cell lines. The proposed binding mode of STK899704 is at the interface between alpha beta-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.

Title:	Anticancer activity of a novel small molecule tubulin inhibitor STK899704
Authors:	Pham, Thi Thu Huong Sakchaisri, Krisada Kim, Sun-Ok; Hwang
Keywords:	MICROTUBULE DYNAMICS DUAL INHIBITORS ACYLHYDRAZONE DERIVATIVES CHROMOSOME CONDENSATION MULTIDRUG-RESISTANCE MAMMALIAN-CELLS GENE-EXPRESSION BINDING AGENTS P-GLYCOPROTEIN HISTONE H3
Issue Date:	2017
Publisher:	PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Citation:	ISIKNOWLEDGE
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 mu M. 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 multi-drug-resistant cancer cell lines. The proposed binding mode of STK899704 is at the interface between alpha beta-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.
Description:	TNS07067 ; PLOS ONE Volume: 12 Issue: 3 Article Number: e0173311 Published: MAR 15 2017
URI:	http://repository.vnu.edu.vn/handle/VNU_123/29664
ISSN:	1932-6203
Appears in Collections:	Bài báo của ĐHQGHN trong Web of Science