Anticancer activity of a novel small molecule tubulin inhibitor STK899704

作者：Sakchaisri Krisada; Kim Sun Ok; Hwang Joonsung; Soung Nak Kyun; Lee Kyung Ho; Choi Tae Woong; Lee Yongjun; Park Chan Mi; Thimmegowda Naraganahalli R; Lee Phil Young; Shwetha Bettaswamigowda; Srinivasrao Ganipisetti; Pham Thi Thu Huong; Jang Jae Hyuk; Yum Hye Won; Surh Young Joon; Lee Kyung S; Park Hwangseo; Kim Seung Jun; Kwon Yong Tae^*; Ahn Jong Seog^*; Kim Bo Yeon^*

来源：PLos One, 2017, 12(3): e0173311.

DOI：10.1371/journal.pone.0173311

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.

• 出版日期2017-3-15
• 单位NIH