PloS one, 2017-03, Vol.12 (3), p.e0173311
- 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
- Lebedeva, Irina V
2017
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- Autor(en) / Beteiligte
- 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
- Lebedeva, Irina V
- Titel
- Anticancer activity of a novel small molecule tubulin inhibitor STK899704
- Ist Teil von
- PloS one, 2017-03, Vol.12 (3), p.e0173311
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0173311Titel-ID: cdi_plos_journals_1877791361
- Format
- –
- Schlagworte
- 5-Fluorouracil, Animals, Anticancer properties, Antineoplastic agents, Antineoplastic Agents - chemistry, Antineoplastic Agents - pharmacology, Antineoplastic drugs, Antitumor activity, Antitumor agents, Apoptosis, Benzofurans - chemistry, Benzofurans - pharmacology, Binding sites, Biology and Life Sciences, Biotechnology, Cancer, Cancer cells, Cancer therapies, Cancer treatment, Carcinogenesis, Carcinogens, cdc25 Phosphatases - metabolism, Cell cycle, Cell Cycle Proteins - metabolism, Cell division, Cell Line, Tumor, Cell proliferation, Cell Proliferation - drug effects, Colchicine, Cyclin B1, Cyclin B1 - metabolism, Depolymerization, Dosage and administration, Doxorubicin, Drugs, Gene expression, Humans, Inhibitors, Kinases, Laboratories, Medical research, Medicine and Health Sciences, Metabolism, Mice, Multidrug resistance, Neurotoxicity, Paclitaxel, Pharmacy, Phosphorylation, Physical Sciences, Polo-like kinase, Polo-Like Kinase 1, Polymerization, Polymerization - drug effects, Protein Serine-Threonine Kinases - metabolism, Proteins, Proto-Oncogene Proteins - metabolism, Research and analysis methods, Skin, Skin cancer, Spindle Apparatus - drug effects, Taxol, Tubulin, Tubulin - metabolism, Tubulin Modulators - chemistry, Tubulin Modulators - pharmacology, Tumor cell lines, Tumors