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Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment...

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Autores principales: Wang, Na-Na, Li, Zhi-Heng, Zhao, He, Tao, Yan-Fang, Xu, Li-Xiao, Lu, Jun, Cao, Lan, Du, Xiao-Juan, Sun, Li-Chao, Zhao, Wen-Li, Xiao, Pei-Fang, Fang, Fang, Su, Guang-Hao, Li, Yan-Hong, Li, Gang, Li, Yi-Ping, Xu, Yun-Yun, Zhou, Hui-Ting, Wu, Yi, Jin, Mei-Fang, Liu, Lin, Ni, Jian, Wang, Jian, Hu, Shao-Yan, Zhu, Xue-Ming, Feng, Xing, Pan, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307303/
https://www.ncbi.nlm.nih.gov/pubmed/25574601
http://dx.doi.org/10.3390/ijms16011266
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author Wang, Na-Na
Li, Zhi-Heng
Zhao, He
Tao, Yan-Fang
Xu, Li-Xiao
Lu, Jun
Cao, Lan
Du, Xiao-Juan
Sun, Li-Chao
Zhao, Wen-Li
Xiao, Pei-Fang
Fang, Fang
Su, Guang-Hao
Li, Yan-Hong
Li, Gang
Li, Yi-Ping
Xu, Yun-Yun
Zhou, Hui-Ting
Wu, Yi
Jin, Mei-Fang
Liu, Lin
Ni, Jian
Wang, Jian
Hu, Shao-Yan
Zhu, Xue-Ming
Feng, Xing
Pan, Jian
author_facet Wang, Na-Na
Li, Zhi-Heng
Zhao, He
Tao, Yan-Fang
Xu, Li-Xiao
Lu, Jun
Cao, Lan
Du, Xiao-Juan
Sun, Li-Chao
Zhao, Wen-Li
Xiao, Pei-Fang
Fang, Fang
Su, Guang-Hao
Li, Yan-Hong
Li, Gang
Li, Yi-Ping
Xu, Yun-Yun
Zhou, Hui-Ting
Wu, Yi
Jin, Mei-Fang
Liu, Lin
Ni, Jian
Wang, Jian
Hu, Shao-Yan
Zhu, Xue-Ming
Feng, Xing
Pan, Jian
author_sort Wang, Na-Na
collection PubMed
description Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC(50)) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC(50) of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined.
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spelling pubmed-43073032015-02-02 Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells Wang, Na-Na Li, Zhi-Heng Zhao, He Tao, Yan-Fang Xu, Li-Xiao Lu, Jun Cao, Lan Du, Xiao-Juan Sun, Li-Chao Zhao, Wen-Li Xiao, Pei-Fang Fang, Fang Su, Guang-Hao Li, Yan-Hong Li, Gang Li, Yi-Ping Xu, Yun-Yun Zhou, Hui-Ting Wu, Yi Jin, Mei-Fang Liu, Lin Ni, Jian Wang, Jian Hu, Shao-Yan Zhu, Xue-Ming Feng, Xing Pan, Jian Int J Mol Sci Article Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC(50)) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC(50) of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined. MDPI 2015-01-07 /pmc/articles/PMC4307303/ /pubmed/25574601 http://dx.doi.org/10.3390/ijms16011266 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Na-Na
Li, Zhi-Heng
Zhao, He
Tao, Yan-Fang
Xu, Li-Xiao
Lu, Jun
Cao, Lan
Du, Xiao-Juan
Sun, Li-Chao
Zhao, Wen-Li
Xiao, Pei-Fang
Fang, Fang
Su, Guang-Hao
Li, Yan-Hong
Li, Gang
Li, Yi-Ping
Xu, Yun-Yun
Zhou, Hui-Ting
Wu, Yi
Jin, Mei-Fang
Liu, Lin
Ni, Jian
Wang, Jian
Hu, Shao-Yan
Zhu, Xue-Ming
Feng, Xing
Pan, Jian
Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells
title Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells
title_full Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells
title_fullStr Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells
title_full_unstemmed Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells
title_short Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells
title_sort molecular targeting of the oncoprotein plk1 in pediatric acute myeloid leukemia: ro3280, a novel plk1 inhibitor, induces apoptosis in leukemia cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307303/
https://www.ncbi.nlm.nih.gov/pubmed/25574601
http://dx.doi.org/10.3390/ijms16011266
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