ABSTRACT
Objective: To investigate anti-tumor effect of rice bran hydrolysates (RBH) on proliferation, migration, invasion, and angiogenesis of cholangiocarcinoma (CCA) cells, and elucidate the underlying mechanisms. Methods: RBH was prepared from Tubtim Chumprae rice (Oryza sativa L.) by hydrothermolysis followed by protease digestion. Phenolic content in RBH was analyzed by high-performance liquid chromatography. Human CCA cells, KKU-156, KKU-452, and KKU-100, were used to study the effects of RBH on proliferation, migration, invasion, and adhesion by wound healing, Transwell chamber, and fibronectin cell adhesion assays. Angiogenesis was evaluated using human umbilical vein endothelial cells. Proteins associated with cancer progression were analyzed by immunobloting assays. Results: RBH contained carbohydrates, proteins, lipids, and various phenolic compounds and flavonoids. RBH did not inhibit CCA proliferation, but strongly suppressed migration, invasion, adhesion of CCA cells, and the formation of tube-like capillary structures of human umbilical vein endothelial cells. Moreover, RBH down-regulated phosphorylation of FAK, PI3K, and Akt, suppressed NF-κB nuclear translocation, decreased the expression of ICAM-1, vimentin and vascular endothelium growth factor (VEGF), and increased the expression of E-cadherin. Conclusions: RBH suppresses CCA cell migration and invasion and decreases expression of proteins involved in cancer metastasis. RBH is a potential food supplement for cancer prevention.
ABSTRACT
Background: Chemotherapeutic treatment of cholangiocarcinoma is largely ineffective, because it is due to non-responsive for the obscured reason of the cancer to anticancer agents. Study was to investigate the cytotoxicity effects of chemotherapeutic agents and curcumin in vitro.Objective: To test sensitivity of cholangiocarcinoma cell lines to chemotherapeutic agents and curcumin Material and Methods: Three cholangiocarcinoma (CCA) cell lines, including KKU-100, KKU-M214 and KKU-OCA17 were used in the study. All cell lines were treated with three chemotherapeutic agents (5-fluorouracil, doxorubicin and carboplatin) or curcumin. The cell viability was determined under a fluorescence microscope by counting the number of living and dead cells after treatment.Results: KKU-100 and KKU-M214 were the very sensitive cell lines to doxorubicin (IC50 values ranging from 0.4 to 0.7 nmol/l), whereas KKU-OCA17 was relatively more resistant cell line. Interestingly, all cell lines were sensitive to curcumin (IC50 values ranging from 3 to 17 μmol/l). Conclusion: This study showed different degrees of semsitivity of CCA cell lines to various chemotherapeutic agents. The data could serve as basic information for chemotherapeutic selection for the treatment in CCA patients. Moreover curcumin exhibits the cytotoxicity on CCA cell lines; thereby it is suggested to be very beneficial in the development of strategy for chemotherapy of CCA cancer.Keywords: cholangiocarcinoma, curcumin, chemotherapeutic agent