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Exp Dermatol. 2018 Mar;27(3):285-288. doi: 10.1111/exd.13506.

A novel tubulin inhibitor STK899704 induces tumor regression in DMBA/TPA-induced skin carcinogenesis model.

Author information

1
Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Korea.
2
Department of Biomolecular Science, University of Science & Technology (UST), Daejeon, Korea.
3
Department of Molecular & Life Science, College of Science & Technology, Hanyang University (ERICA), Ansan, Korea.
4
College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea.
5
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
6
Department of Biomedical Sciences and Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, Korea.

Abstract

Skin cancer is the most common type of cancer. The incidence rate of skin cancer has continuously increased over the past decades. In an effort to discover novel anticancer agents, we identified a novel tubulin inhibitor STK899704, which is structurally distinct from other microtubule-binding agents such as colchicine, vinca alkaloids and taxanes. STK899704 inhibited microtubule polymerization leading to mitotic arrest and suppressed the proliferation of various cancer cell lines as well as multidrug resistance cancer cell lines. In this study, our investigation is further extended into animal model to evaluate the effect of STK899704 on skin carcinogenesis in vivo. Surprisingly, almost 80% of the tumors treated with STK899704 were regressed with a one-fifth reduction in tumor volume. Furthermore, the efficacy of STK899704 was nearly 2 times higher than that of 5-fluorouracil, a widely used skin cancer therapeutic. Overall, our results suggest that STK899704 is a promising anticancer chemotherapeutic that may replace existing therapies, particularly for skin cancer.

KEYWORDS:

STK899704; anticancer therapy; mitotic inhibitor; skin cancer; tubulin inhibitor

PMID:
29392819
DOI:
10.1111/exd.13506
[Indexed for MEDLINE]

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