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 |
Nhận xét
Đăng nhận xét