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Garcinol downregulates Notch1 signaling via modulating miR‐200c and suppresses oncogenic properties of PANC‐1 cancer stem‐like cells
Author(s) -
Huang ChiCheng,
Lin ChienMin,
Huang YanJiun,
Wei Li,
Ting LeiLi,
Kuo ChiaChun,
Hsu Cheyu,
Chiou JengFong,
Wu Alexander T. H.,
Lee WeiHwa
Publication year - 2017
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1002/bab.1446
Subject(s) - cancer stem cell , cd44 , pancreatic cancer , downregulation and upregulation , cancer research , side population , stem cell , gemcitabine , abcg2 , cancer , microrna , cell culture , population , sox2 , biology , chemistry , cell , medicine , microbiology and biotechnology , transcription factor , transporter , biochemistry , atp binding cassette transporter , genetics , environmental health , gene
Pancreatic cancer represents one of the most aggressive types of malignancy due to its high resistance toward most clinically available treatments. The presence of pancreatic cancer stem‐like cells (CSCs) has been attributed to the intrinsically high resistance and highly metastatic potential of this disease. Here, we identified and isolated pancreatic CSCs using the side population (SP) method from human pancreatic cancer cell line, PANC‐1. We then compared the SP and non‐SP PANC‐1 cells genetically. PANC‐1 SP cells exhibited CSC properties including enhanced self‐renewal ability, increased metastatic potential, and resistance toward gemcitabine treatment. These cancer stem‐like phenotypes were supported by their enhanced expression of ABCG2, Oct4, and CD44. A traditional plant‐derived antioxidant, garcinol, has been implicated for its anticancer properties. Here, we found that garcinol treatment to PANC‐1 SP cells significantly suppressed the stem‐like properties of PANC‐1 SP cells and metastatic potential by downregulating the expression of Mcl‐1, EZH2, ABCG2, Gli‐1, and Notch1. More importantly, garcinol treatment led to the upregulation of several tumor suppressor microRNAs, and miR‐200c increased by garcinol treatment was found to target and downregulate Notch1. Thus, PANC‐1 SP cells may serve as a model for studying drug‐resistant pancreatic CSCs, and garcinol has the potential as an antagonist against pancreatic CSCs.