Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment

Abstract

Cholangiocarcinoma (CCA) is a major cause of mortality in Northeast Thailand with about 14,000 deaths each year. There is an urgent necessity for novel drug discovery to increase effective treatment possibilities. A recent study reported that lignin derived from Scoparia dulcis can cause CCA cell inhibition. However, there is no evidence on the inhibitory effect of coniferyl alcohol (CA), which is recognized as a major monolignol-monomer forming a very complex structure of lignin. Therefore, we aimed to investigate the effect of CA on CCA cell apoptosis. We demonstrated that a half-inhibitory concentration of CA on KKU-100 cells at 48 h and 72 h was 361.87 ± 30.58 and 268.27 ± 18.61 μg/mL, respectively, and on KKU-213 cells 184.37 ± 11.15 and 151.03 ± 24.99 μg/mL, respectively. Furthermore, CA induced CCA cell apoptosis as demonstrated by annexin V/PI staining in correspondence with an increase in the BAX/Bcl-2 ratio. A metabonomic study indicated that CA significantly decreased the intracellular concentrations of glutathione and succinate in KKU-213 cells and increased dihydrogen acetone phosphate levels in KKU-100 cells treated with 200 µg/mL of CA compared to the control group. In conclusion, CA induced cellular metabolic changes which are involved in the antioxidant defense mechanism, glycerophospholipid metabolism and the tricarboxylic acid cycle. CA may serve as a potent anticancer agent for CCA treatment by inducing CCA cellular apoptosis.

Inhibition of Ceramide Glycosylation Enhances Cisplatin Sensitivity in Cholangiocarcinoma by Limiting the Activation of the ERK Signaling Pathway

“…KKU-100 is a slow growing cell line that was established from a perihilar-CCA-containing wild type TP53 and mutant Kras, whereas KKU-213 is a highly aggressive CCA cell line which was established from intrahepatic CCA containing both TP53 and Kras mutations [ 24 , 25 ]. These findings agree with other studies on gemcitabine treatment and other anticancer agents, in which intracellular metabolic alterations and/or different mechanisms of drug resistance determine the differential response of each CCA cell line to particular chemotherapeutic agents [ 26 , 43 , 44 , 45 ].…”

Pd-Catalyzed Aerobic Synthesis of Allylic Sulfones from Allylic Alcohols and Sulfonyl Hydrazines in Water

“…Moreover, the reaction of cinnamyl alcohol ( 1a ) and 4-methylbenzenesulfonyl hydrazine ( 2a ) was carried out in gram scale at 60 °C, still affording the target 3aa in 89% yield (1.21 g), showing the practicability of this new method (eq ). Finally, the biologically active coniferyl alcohol ( 1p ) was investigated; the reaction proceeded smoothly to afford the target 3ap in yield of 76%, further showing the practicability of this new method (eq ). Control reactions were then carried out to probe the reaction mechanism.…”