PUBLICATION
Isoquinoline Alkaloids from Coptis chinensis Franch: Focus on Coptisine as a Potential Therapeutic Candidate against Gastric Cancer Cells
- Authors
- Nakonieczna, S., Grabarska, A., Gawel, K., Wróblewska-Łuczka, P., Czerwonka, A., Stepulak, A., Kukula-Koch, W.
- ID
- ZDB-PUB-220924-15
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(18): (Journal)
- Registered Authors
- Gawel, Kinga Aurelia
- Keywords
- CPC chromatography technique, Coptis chinensis Franch, berberine, coptisine, gastric cancer, isoquinoline alkaloids, jatrorrhizine, palmatine, zebrafish
- MeSH Terms
-
- Alkaloids*/analysis
- Alkaloids*/pharmacology
- Animals
- Berberine*/analogs & derivatives
- Berberine*/pharmacology
- Berberine Alkaloids*/pharmacology
- Bromodeoxyuridine
- Chloroform
- Cisplatin
- Coptis*/chemistry
- Coptis chinensis
- Drugs, Chinese Herbal*/chemistry
- Hydrochloric Acid
- Isoquinolines
- Methanol
- Solvents
- Stomach Neoplasms*/drug therapy
- Water
- Zebrafish
- PubMed
- 36142236 Full text @ Int. J. Mol. Sci.
Citation
Nakonieczna, S., Grabarska, A., Gawel, K., Wróblewska-Łuczka, P., Czerwonka, A., Stepulak, A., Kukula-Koch, W. (2022) Isoquinoline Alkaloids from Coptis chinensis Franch: Focus on Coptisine as a Potential Therapeutic Candidate against Gastric Cancer Cells. International Journal of Molecular Sciences. 23(18).
Abstract
Gastric cancer (GC) has high incidence rates and constitutes a common cause of cancer mortality. Despite advances in treatment, GC remains a challenge in cancer therapy which is why novel treatment strategies are needed. The interest in natural compounds has increased significantly in recent years because of their numerous biological activities, including anti-cancer action. The isolation of the bioactive compounds from Coptis chinensis Franch was carried out with the Centrifugal Partition Chromatography (CPC) technique, using a biphasic solvent system composed of chloroform (CHCl3)-methanol (MeOH)-water (H2O) (4:3:3, v/v) with an addition of hydrochloric acid and trietylamine. The identity of the isolated alkaloids was confirmed using a high resolution HPLC-MS chromatograph. The phytochemical constituents of Coptis chinensis such as berberine, jatrorrhizine, palmatine and coptisine significantly inhibited the viability and growth of gastric cancer cell lines ACC-201 and NCI-N87 in a dose-dependent manner, with coptisine showing the highest efficacy as revealed using MTT and BrdU assays, respectively. Flow cytometry analysis confirmed the coptisine-induced population of gastric cancer cells in sub-G1 phase and apoptosis. The combination of coptisine with cisplatin at the fixed-ratio of 1:1 exerted synergistic and additive interactions in ACC-201 and NCI-N87, respectively, as determined by means of isobolographic analysis. In in vivo assay, coptisine was safe for developing zebrafish at the dose equivalent to the highest dose active in vitro, but higher doses (greater than 10 times) caused morphological abnormalities in larvae. Our findings provide a theoretical foundation to further studies on more detailed mechanisms of the bioactive compounds from Coptis chinensis Franch anti-cancer action that inhibit GC cell survival in in vitro settings.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping