Original Research ARTICLE
The Novel Small Molecule STK899704 Promotes Senescence of the Human A549 NSCLC Cells by Inducing DNA Damage Responses and Cell Cycle Arrest
- 1Department of Bioscience and Biotechnology, Konkuk University, South Korea
- 2Protein Metabolism Medical Research Center and Department of Biomedical Sciences, Seoul National University, South Korea
- 3World Class Institute (WCI), Anticancer Agents Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), South Korea
- 4Department of Bacteriology, Molecular and Environmental Toxicology Center (METC), University of Wisconsin-Madison, United States
- 5College of Pharmacy and Medical Research Center, Chungbuk National University, South Korea
The novel synthetic compound designated STK899704 (PubChem CID: 5455708) suppresses the proliferation of a broad range of cancer cell types. However, the details of its effect on lung cancer cells are unclear. We investigated the precise anticancer effect of STK899704 on senescence and growth arrest of A549 human non-small cell lung cancer (NSCLC) cells. STK899704 affected NSCLC cell cycle progression and decreased cell viability in a dose-dependent manner. Immunofluorescence staining revealed that STK899704 destabilized microtubules. Cell cycle analysis showed an increase in the population of NSCLC cells in the sub-G1 and G2/M phases, indicating that STK899704 might cause DNA damage via tubulin aggregation. Furthermore, we observed increased mitotic catastrophe in STK899704-treated cells. As STK899704 led to elevated levels of the p53 pathway-associated proteins, it would likely affect the core DNA damage response pathway. Moreover, STK899704 promoted senescence of NSCLC cells by inducing the p53-associated DNA damage response pathways. These findings suggest that the novel anti-proliferative small molecule STK899704 promotes cell death by inducing DNA damage response pathways and senescence after cell cycle arrest, being a potential drug for treating human lung cancers.
Keywords: Lung carcinoma, STK899704, senescence, cancer therapy, cell cycle arrest, p53
Received: 22 Sep 2017;
Accepted: 14 Feb 2018.
Edited by:David A. Gewirtz, Virginia Commonwealth University, United States
Reviewed by:Fernando Rodríguez-Serrano, University of Granada, Spain
Lawrence Panasci, Segal Cancer Centre, Canada
Copyright: © 2018 Park, Bak, Kim, Srinivasrao, Hwang, Sung, Kim, Yu, Hong and Yoon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Do-Young Yoon, Konkuk University, Department of Bioscience and Biotechnology, 120, Neungdong-ro, Gwangjin-gu, Seoul, 05059, South Korea, firstname.lastname@example.org