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Open AccessArticle

Protein Expression Profiling Identifies Key Proteins and Pathways Involved in Growth Inhibitory Effects Exerted by Guggulsterone in Human Colorectal Cancer Cells

1
Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar
2
Department of Pharmaceutical Sciences, College of Pharmacy, Qatar University, Doha 2713, Qatar
3
Department of Dermatology and Venereology, Hamad Medical Corporation, Doha 3050, Qatar
4
Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, Doha 24144, Qatar
5
Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA
6
College of Medicine, Qatar University, Doha 2713, Qatar
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1478; https://doi.org/10.3390/cancers11101478
Received: 25 August 2019 / Revised: 19 September 2019 / Accepted: 24 September 2019 / Published: 1 October 2019
(This article belongs to the Special Issue Apoptosis in Cancer)
Colorectal cancer (CRC) is a leading killer cancer worldwide and one of the most common malignancies with increasing incidences of mortality. Guggulsterone (GS) is a plant sterol used for treatment of various ailments such as obesity, hyperlipidemia, diabetes, and arthritis. In the current study, anti-cancer effects of GS in human colorectal cancer cell line HCT 116 was tested, potential targets identified using mass spectrometry-based label-free shotgun proteomics approach and key pathways validated by proteome profiler antibody arrays. Comprehensive proteomic profiling identified 14 proteins as significantly dysregulated. Proteins involved in cell proliferation/migration, tumorigenesis, cell growth, metabolism, and DNA replication were downregulated while the protein with functional role in exocytosis/tumor suppression was found to be upregulated. Our study evidenced that GS treatment altered expression of Bcl-2 mediated the mitochondrial release of cytochrome c which triggered the formation of apoptosome as well as activation of caspase-3/7 leading to death of HCT 116 cells via intrinsic apoptosis pathway. GS treatment also induced expression of p53 protein while p21 expression was unaltered with no cell cycle arrest. In addition, GS was found to inhibit NF-kB signaling in colon cancer cells by quelling the expression of its regulated gene products Bcl-2, cIAP-1, and survivin.
Keywords: colorectal cancer; HCT 116; SW620; guggulsterone; label-free shotgun proteomics; intrinsic apoptosis pathway; NF-kB signaling colorectal cancer; HCT 116; SW620; guggulsterone; label-free shotgun proteomics; intrinsic apoptosis pathway; NF-kB signaling
MDPI and ACS Style

Leo, R.; Therachiyil, L.; Siveen, S.K.; Uddin, S.; Kulinski, M.; Buddenkotte, J.; Steinhoff, M.; Krishnankutty, R. Protein Expression Profiling Identifies Key Proteins and Pathways Involved in Growth Inhibitory Effects Exerted by Guggulsterone in Human Colorectal Cancer Cells. Cancers 2019, 11, 1478.

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