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Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells.
Int J Mol Sci. 2015 Dec 29; 17(1)IJ

Abstract

Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G₂/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5' AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.

Authors+Show Affiliations

Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated to Southern Medical University, Guangdong 528300, China. rbjsdyy@outlook.com. Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612, USA. rbjsdyy@outlook.com.Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612, USA. zzhou1@health.usf.edu.Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated to Southern Medical University, Guangdong 528300, China. zdjsdyy@outlook.com.Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated to Southern Medical University, Guangdong 528300, China. jylsdyy@outlook.com.Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated to Southern Medical University, Guangdong 528300, China. wjhsdyy@outlook.com.Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated to Southern Medical University, Guangdong 528300, China. oymzsdyy@outlook.com.Department of Gastrointestinal Surgery, Shunde First People's Hospital Affiliated to Southern Medical University, Guangdong 528300, China. cxwsdyy@outlook.com.Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612, USA. szhou@health.usf.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26729093

Citation

Ren, Bao-Jun, et al. "Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells." International Journal of Molecular Sciences, vol. 17, no. 1, 2015.
Ren BJ, Zhou ZW, Zhu DJ, et al. Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells. Int J Mol Sci. 2015;17(1).
Ren, B. J., Zhou, Z. W., Zhu, D. J., Ju, Y. L., Wu, J. H., Ouyang, M. Z., Chen, X. W., & Zhou, S. F. (2015). Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells. International Journal of Molecular Sciences, 17(1). https://doi.org/10.3390/ijms17010041
Ren BJ, et al. Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells. Int J Mol Sci. 2015 Dec 29;17(1) PubMed PMID: 26729093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells. AU - Ren,Bao-Jun, AU - Zhou,Zhi-Wei, AU - Zhu,Da-Jian, AU - Ju,Yong-Le, AU - Wu,Jin-Hao, AU - Ouyang,Man-Zhao, AU - Chen,Xiao-Wu, AU - Zhou,Shu-Feng, Y1 - 2015/12/29/ PY - 2015/11/02/received PY - 2015/12/07/revised PY - 2015/12/09/accepted PY - 2016/1/6/entrez PY - 2016/1/6/pubmed PY - 2016/10/26/medline KW - EMT KW - alisertib KW - cell cycle KW - colorectal cancer KW - programmed cell death JF - International journal of molecular sciences JO - Int J Mol Sci VL - 17 IS - 1 N2 - Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G₂/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5' AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/26729093/Alisertib_Induces_Cell_Cycle_Arrest_Apoptosis_Autophagy_and_Suppresses_EMT_in_HT29_and_Caco_2_Cells_ L2 - https://www.mdpi.com/resolver?pii=ijms17010041 DB - PRIME DP - Unbound Medicine ER -