Abstract Title:

Garcinol downregulates Notch1 signaling via modulating miR-200c and suppresses oncogenic properties of PANC-1 cancer stem-like cells.

Abstract Source:

Biotechnol Appl Biochem. 2015 Sep 24. Epub 2015 Sep 24. PMID: 26400206

Abstract Author(s):

Chi-Cheng Huang, Chien-Min Lin, Yan-Jiun Huang, Li Wei, Lei-Li Ting, Chia-Chun Kuo, Cheyu Hsu, Chiou Jf, Alexander Th Wu, Wei-Hwa Lee

Article Affiliation:

Chi-Cheng Huang


Pancreatic cancer represents one of the most aggressive types of malignancy due to its high resistance towards most clinically available treatments. The presence of pancreatic cancer stem-like cells (CSCs) have been attributed to the intrinsically high resistance and highly metastatic potential of this disease. Here, we identified and isolated pancreatic cancer stem-like cells using 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 cancer stem-like cell properties including enhanced self-renewal ability, increased metastatic potential and resistance towards gemcitabine treatment. These cancer stem-like phenotypes were supported by their enhanced expression of ABCG2, Oct4 and CD44. A traditional plant-derived anti-oxidant, garcinol, have been implicated for its anti-cancer 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 down-regulating the expression of Mcl-1, EZH2, ABCG2, Gli-1 and Notch1. More importantly, garcinol treatment led to the up-regulation of several tumor suppressor miRNAs and miR-200c increased by garcinol treatment was found to target and down-regulate Notch1. Thus, PANC-1 SP cells may serve as a model for studying drug-resistant pancreatic cancer stem-like cells and garcinol has the potential as an antagonist against pancreatic CSCs. This article is protected by copyright. All rights reserved.

Study Type : In Vitro Study

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