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AuthorLeo R.
AuthorTherachiyil L.
AuthorSiveen S.K.
AuthorUddin S.
AuthorKulinski M.
AuthorBuddenkotte J.
AuthorSteinhoff M.
AuthorKrishnankutty R.
Available date2020-04-09T07:35:02Z
Publication Date2019
Publication NameCancers
ResourceScopus
ISSN20726694
URIhttp://dx.doi.org/10.3390/cancers11101478
URIhttp://hdl.handle.net/10576/13960
AbstractColorectal 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. - 2019 by the authors. Licensee MDPI, Basel, Switzerland.
SponsorFunding: This study was funded by MEDICAL RESEARCH CENTER (MRC) at HAMAD MEDICAL CORPORATION, Doha, State of Qatar with grant number MRC#15264/15.
Languageen
PublisherMDPI AG
SubjectColorectal cancer
Guggulsterone
HCT 116
Intrinsic apoptosis pathway
Label-free shotgun proteomics
NF-kB signaling
SW620
TitleProtein expression profiling identifies key proteins and pathways involved in growth inhibitory effects exerted by guggulsterone in human colorectal cancer cells
TypeArticle
Issue Number10
Volume Number11
dc.accessType Open Access


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