Author:
Jantawong Chanakan,Chamgramol Yaovalux,Intuyod Kitti,Priprem Aroonsri,Pairojkul Chawalit,Klungsaeng Sirinapha,Dangtakot Rungtiwa,Pongking Thatsanapong,Sitthirach Chutima,Pinlaor Porntip,Waraasawapati Sakda,Pinlaor Somchai
Abstract
Abstract
Background
Curcumin-loaded nanocomplexes (CNCs) previously demonstrated lower toxicity and extended release better than is the case for free curcumin. Here, we evaluated the efficacy of CNCs against opisthorchiasis-associated cholangiocarcinoma (CCA) in hamsters.
Method
Dose optimization (dose and frequency) was performed over a 1-month period using hamsters, a model that is widely used for study of opisthorchiasis-associated cholangiocarcinoma. In the main experimental study, CCA was induced by a combination of fluke, Opisthorchis viverrini (OV), infection and N-nitrosodimethylamine (NDMA) treatment. Either blank (empty) nanocomplexes (BNCs) or different concentrations of CNCs (equivalent to 10 and 20 mg cur/kg bw) were given to hamsters thrice a week for 5 months. The histopathological changes, biochemical parameters, and the expression of inflammatory/oncogenic transcription factors were investigated. In addition, the role of CNCs in attenuating CCA genesis, as seen in an animal model, was also confirmed in vitro using CCA cell lines.
Results
The optimization study revealed that treatment with CNCs at a dose equivalent to 10 mg cur/kg bw, thrice a week for 1 month, led to a greater reduction of inflammation and liver injury induced in hamsters by OV + NDMA than did treatments at other dose rates. Oral administration with CNCs (10 mg cur/kg bw), thrice a week for 5 months, significantly increased survival rate, reduced CCA incidence, extent of tumor development, cholangitis, bile duct injury and cholangiofibroma. In addition, this treatment decreased serum ALP and ALT activities and suppressed expression of NF-κB, FOXM1, HMGB1, PCNA and formation of 8-nitroguanine. Treatment of CCA cell lines with CNCs also reduced cell proliferation and colony formation, similar to those treated with NF-κB and/or FOXM1 inhibitors.
Conclusion
CNCs (10 mg cur/kg bw) attenuate the progression of fluke-related CCA in hamsters partly via a NF-κB and FOXM1-mediated pathway.
Funder
Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand
Basic Research Fund of Khon Kaen University under Cholangiocarcinoma Research Institute
Center of Excellence on Medical Biotechnology (CEMB), S&T Postgraduate Education and Research Development Office (PERDO), Office of Higher Education Commission (OHEC), Thailand
Publisher
Springer Science and Business Media LLC
Subject
Physical and Theoretical Chemistry,Pharmaceutical Science,Oncology,Biomedical Engineering