Discovering proteins for chemoprevention and chemotherapy by curcumin in liver fluke infection-induced bile duct cancer

Khoontawad, Jarinya, Intuyod, Kitti, Rucksaken, Rucksak, Hongsrichan, Nuttanan, Pairojkul, Chawalit, Pinlaor, Porntip, Boonmars, Thidarut, Wongkham, Chaisiri, Jones, Alun, Plieskatt, Jordan, Potriquet, Jeremy, Bethony, Jeffrey M., Mulvenna, Jason, and Pinlaor, Somchai (2018) Discovering proteins for chemoprevention and chemotherapy by curcumin in liver fluke infection-induced bile duct cancer. PLoS One, 13 (11). e0207405.

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Abstract

Modulation or prevention of protein changes during the cholangiocarcinoma (CCA) process induced by Opisthorchis viverrini (Ov) infection may become a key strategy for prevention and treatment of CCA. Monitoring of such changes could lead to discovery of protein targets for CCA treatment. Curcumin exerts anti-inflammatory and anti-CCA activities partly through its protein-modulatory ability. To support the potential use of curcumin and to discover novel target molecules for CCA treatment, we used a quantitative proteomic approach to investigate the effects of curcumin on protein changes in an Ov-induced CCA-harboring hamster model. Isobaric labelling and tandem mass spectrometry were used to compare the protein expression profiles of liver tissues from CCA hamsters with or without curcumin dietary supplementation. Among the dysregulated proteins, five were upregulated in liver tissues of CCA hamsters but markedly downregulated in the CCA hamsters supplemented with curcumin: S100A6, lumican, plastin-2, 14-3-3 zeta/delta and vimentin. Western blot and immunohistochemical analyses also showed similar expression patterns of these proteins in liver tissues of hamsters in the CCA and CCA + curcumin groups. Proteins such as clusterin and S100A10, involved in the NF-kappa B signaling pathway, an important signaling cascade involved in CCA genesis, were also upregulated in CCA hamsters and were then suppressed by curcumin treatment. Taken together, our results demonstrate the important changes in the proteome during the genesis of O. viverrini-induced CCA and provide an insight into the possible protein targets for prevention and treatment of this cancer.

Item ID: 56508
Item Type: Article (Research - C1)
ISSN: 1932-6203
Copyright Information: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Funders: Higher Education Research Promotion and National Research University Project of Thailand, Higher Education Commission - Health Cluster (HECHC), Cholangiocarcinoma Screening and Care Program (CASCAP), National Cancer Institute (NCI), National Institute of Allergy and Infectious Disease (NIAID), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: HECHC - SHeP-GMS; PD55208, HECHC - SHeP-GMS; NRU572004, NCI R01CA155297, NIAID P50AI098639, NHMRC 1051627
Date Deposited: 05 Dec 2018 07:52
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 100%
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