Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment
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 <i>Scoparia dulcis</i> ca...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/3/476 |
| _version_ | 1827697002530471936 |
|---|---|
| author | Bundit Promraksa Praewpan Katrun Jutarop Phetcharaburanin Yingpinyapat Kittirat Nisana Namwat Anchalee Techasen Jia V. Li Watcharin Loilome |
| author_facet | Bundit Promraksa Praewpan Katrun Jutarop Phetcharaburanin Yingpinyapat Kittirat Nisana Namwat Anchalee Techasen Jia V. Li Watcharin Loilome |
| author_sort | Bundit Promraksa |
| collection | DOAJ |
| description | 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 <i>Scoparia dulcis</i> 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. |
| first_indexed | 2024-03-10T13:00:10Z |
| format | Article |
| id | doaj.art-9692ea8949b4460192148c9cf6bc1616 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T13:00:10Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-9692ea8949b4460192148c9cf6bc16162023-11-21T11:34:58ZengMDPI AGBiomolecules2218-273X2021-03-0111347610.3390/biom11030476Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol TreatmentBundit Promraksa0Praewpan Katrun1Jutarop Phetcharaburanin2Yingpinyapat Kittirat3Nisana Namwat4Anchalee Techasen5Jia V. Li6Watcharin Loilome7Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandCenter of Excellence for Innovation in Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, UKDepartment of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma (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 <i>Scoparia dulcis</i> 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.https://www.mdpi.com/2218-273X/11/3/476coniferyl alcoholmetabonomicscholangiocarcinoma |
| spellingShingle | Bundit Promraksa Praewpan Katrun Jutarop Phetcharaburanin Yingpinyapat Kittirat Nisana Namwat Anchalee Techasen Jia V. Li Watcharin Loilome Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment Biomolecules coniferyl alcohol metabonomics cholangiocarcinoma |
| title | Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment |
| title_full | Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment |
| title_fullStr | Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment |
| title_full_unstemmed | Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment |
| title_short | Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment |
| title_sort | metabolic changes of cholangiocarcinoma cells in response to coniferyl alcohol treatment |
| topic | coniferyl alcohol metabonomics cholangiocarcinoma |
| url | https://www.mdpi.com/2218-273X/11/3/476 |
| work_keys_str_mv | AT bunditpromraksa metabolicchangesofcholangiocarcinomacellsinresponsetoconiferylalcoholtreatment AT praewpankatrun metabolicchangesofcholangiocarcinomacellsinresponsetoconiferylalcoholtreatment AT jutaropphetcharaburanin metabolicchangesofcholangiocarcinomacellsinresponsetoconiferylalcoholtreatment AT yingpinyapatkittirat metabolicchangesofcholangiocarcinomacellsinresponsetoconiferylalcoholtreatment AT nisananamwat metabolicchangesofcholangiocarcinomacellsinresponsetoconiferylalcoholtreatment AT anchaleetechasen metabolicchangesofcholangiocarcinomacellsinresponsetoconiferylalcoholtreatment AT jiavli metabolicchangesofcholangiocarcinomacellsinresponsetoconiferylalcoholtreatment AT watcharinloilome metabolicchangesofcholangiocarcinomacellsinresponsetoconiferylalcoholtreatment |