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Int. J. Mol. Sci. 2016, 17(1), 41; doi:10.3390/ijms17010041

Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells

1
Department of Gastrointestinal Surgery, Shunde First People’s Hospital Affiliated to Southern Medical University, Guangdong 528300, China
2
Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 2 November 2015 / Revised: 7 December 2015 / Accepted: 9 December 2015 / Published: 29 December 2015
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
View Full-Text   |   Download PDF [8030 KB, uploaded 29 December 2015]   |  

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. View Full-Text
Keywords: alisertib; colorectal cancer; cell cycle; programmed cell death; EMT alisertib; colorectal cancer; cell cycle; programmed cell death; EMT
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ren, B.-J.; Zhou, Z.-W.; Zhu, D.-J.; Ju, Y.-L.; Wu, J.-H.; Ouyang, M.-Z.; Chen, X.-W.; Zhou, S.-F. Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells. Int. J. Mol. Sci. 2016, 17, 41.

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