Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells.

Autor: Milutinović MG; Faculty of Science, Department of Biology and Ecology, University of Kragujevac, Radoja Domanovića 12, 34000, Kragujevac, Serbia. Electronic address: milenagen@gmail.com., Maksimović VM; Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, 11030, Belgrade, Serbia., Cvetković DM; Faculty of Science, Department of Biology and Ecology, University of Kragujevac, Radoja Domanovića 12, 34000, Kragujevac, Serbia., Nikodijević DD; Faculty of Science, Department of Biology and Ecology, University of Kragujevac, Radoja Domanovića 12, 34000, Kragujevac, Serbia., Stanković MS; Faculty of Science, Department of Biology and Ecology, University of Kragujevac, Radoja Domanovića 12, 34000, Kragujevac, Serbia., Pešić M; Institute for Biological Research 'Sinisa Stankovic', University of Belgrade, Despota Stefana 142, 11060, Belgrade, Serbia., Marković SD; Faculty of Science, Department of Biology and Ecology, University of Kragujevac, Radoja Domanovića 12, 34000, Kragujevac, Serbia.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2019 Aug 10; Vol. 240, pp. 111951. Date of Electronic Publication: 2019 May 11.
DOI: 10.1016/j.jep.2019.111951
Abstrakt: Ethnopharmacological Relevance: Teucrum chamaedrys L. is one of the known medicinal plants, useful for treatment of various health problems, especially digestive. In this study, we investigated methanol, ethyl-acetate and acetone extracts of T. chamaedrys in respect to their anticancer properties in SW480 colorectal cancer cells.
Materials and Methods: Cytotoxicity and proapoptotic potential were assessed by MTT cell viability assay and AO/EB double staining. Molecular mechanisms of induced apoptosis were determined by monitoring Fas receptor protein expression through immunofluorescence, Caspase 8 and 9 activity, as well as concentrations of O 2 .- spectrophotometrically. Additionally, mRNA expression of biotransformation enzymes (CYP1A1, CYP1B1, GSTP1) and membrane transporters (MRP1 and MRP2) involved in drug resistance were investigated by qPCR method. Qualitative analysis of individual phenolic compounds was performed by reversed phase HPLC-MS analysis.
Results: Methanol extract shows the best cytotoxicity and selectivity compared to ethyl-acetate and acetone extracts, mainly causing apoptosis of SW480 cells, without affecting normal HaCaT keratinocytes. The increased expression of Fas receptor protein and caspase 8 activity indicate that the death receptor-mediated pathway plays a crucial role in the observed apoptosis. The increased caspase 9 activity and O 2 .- concentration suggest that mitochondria are also involved in the apoptosis. T. chamaedrys methanol extract inhibits mRNA expression of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 in SW480 cells.
Conclusions: Induction of apoptosis and inhibition of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 mRNA expression implies that T. chamaedrys can serve as a valuable source of bioactive compounds as dietary supplements or selective anticancer agents, with the ability to induce apoptosis and modulate drug resistance in colorectal cancer cells.
(Copyright © 2019. Published by Elsevier B.V.)
Databáze: MEDLINE
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