Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction
Background: Cancer is still a major public health issue worldwide, and new therapeutics with anti-tumor activity are still urgently needed. Methods: The anti-tumor activity of TH-39, which shows potent anti-proliferative activity against K562 cells with an IC50 of 0.78 µM, was investigated using imm...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2016-11-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/452546 |
| _version_ | 1818135000180064256 |
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| author | Yongxia Zhu Wei Wei Tinghong Ye Zhihao Liu Li Liu Yong Luo Lidan Zhang Chao Gao Ningyu Wang Luoting Yu |
| author_facet | Yongxia Zhu Wei Wei Tinghong Ye Zhihao Liu Li Liu Yong Luo Lidan Zhang Chao Gao Ningyu Wang Luoting Yu |
| author_sort | Yongxia Zhu |
| collection | DOAJ |
| description | Background: Cancer is still a major public health issue worldwide, and new therapeutics with anti-tumor activity are still urgently needed. Methods: The anti-tumor activity of TH-39, which shows potent anti-proliferative activity against K562 cells with an IC50 of 0.78 µM, was investigated using immunoblot, co-immunoprecipitation, the MTT assay, and flow cytometry. Results: Mechanistically, TH-39 may disrupt the interaction between Hec1 and Nek2 in K562 cells. Moreover, TH-39 inhibited cell proliferation in a concentration- and time-dependent manner by influencing the morphology of K562 cells and inducing G0/G1 phase arrest. G0/G1 phase arrest was associated with down-regulation of CDK2-cyclin E complex and CDK4/6-cyclin D complex activities. Furthermore, TH-39 also induced cell apoptosis, which was associated with activation of caspase-3, down-regulation of Bcl-2 expression and up-regulation of Bax. TH-39 could also decrease mitochondrial membrane potential (Δψm) and increase reactive oxygen species (ROS) accumulation in K562 cells. The results indicated that TH-39 might induce apoptosis via the ROS-mitochondrial apoptotic pathway. Conclusion: This study highlights the potential therapeutic efficacy of the anti-cancer compound TH-39 in treatment-resistant chronic myeloid leukemia. |
| first_indexed | 2024-12-11T09:17:33Z |
| format | Article |
| id | doaj.art-b46851583195440bae0fe82750f1fab8 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-11T09:17:33Z |
| publishDate | 2016-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-b46851583195440bae0fe82750f1fab82022-12-22T01:13:20ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-11-01401-229730810.1159/000452546452546Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis InductionYongxia ZhuWei WeiTinghong YeZhihao LiuLi LiuYong LuoLidan ZhangChao GaoNingyu WangLuoting YuBackground: Cancer is still a major public health issue worldwide, and new therapeutics with anti-tumor activity are still urgently needed. Methods: The anti-tumor activity of TH-39, which shows potent anti-proliferative activity against K562 cells with an IC50 of 0.78 µM, was investigated using immunoblot, co-immunoprecipitation, the MTT assay, and flow cytometry. Results: Mechanistically, TH-39 may disrupt the interaction between Hec1 and Nek2 in K562 cells. Moreover, TH-39 inhibited cell proliferation in a concentration- and time-dependent manner by influencing the morphology of K562 cells and inducing G0/G1 phase arrest. G0/G1 phase arrest was associated with down-regulation of CDK2-cyclin E complex and CDK4/6-cyclin D complex activities. Furthermore, TH-39 also induced cell apoptosis, which was associated with activation of caspase-3, down-regulation of Bcl-2 expression and up-regulation of Bax. TH-39 could also decrease mitochondrial membrane potential (Δψm) and increase reactive oxygen species (ROS) accumulation in K562 cells. The results indicated that TH-39 might induce apoptosis via the ROS-mitochondrial apoptotic pathway. Conclusion: This study highlights the potential therapeutic efficacy of the anti-cancer compound TH-39 in treatment-resistant chronic myeloid leukemia.http://www.karger.com/Article/FullText/452546TH-39Hec1/Nek2K562 cellsG0/G1 cell cycle arrestApoptosis |
| spellingShingle | Yongxia Zhu Wei Wei Tinghong Ye Zhihao Liu Li Liu Yong Luo Lidan Zhang Chao Gao Ningyu Wang Luoting Yu Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction Cellular Physiology and Biochemistry TH-39 Hec1/Nek2 K562 cells G0/G1 cell cycle arrest Apoptosis |
| title | Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction |
| title_full | Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction |
| title_fullStr | Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction |
| title_full_unstemmed | Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction |
| title_short | Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction |
| title_sort | small molecule th 39 potentially targets hec1 nek2 interaction and exhibits antitumor efficacy in k562 cells via g0 g1 cell cycle arrest and apoptosis induction |
| topic | TH-39 Hec1/Nek2 K562 cells G0/G1 cell cycle arrest Apoptosis |
| url | http://www.karger.com/Article/FullText/452546 |
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