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(center dot-) 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(center dot-) concentration suggest that mitochondria are also involved in the apoptosis. T. chamaedrys methanol extract inhibits mRNA expression of CYP1A1, CYPIBI, 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.
TY - JOUR
AU - Milutinović, Milena
AU - Maksimović, Vuk
AU - Cvetković, Danijela M.
AU - Nikodijević, Danijela D.
AU - Stanković, Milan
AU - Pesic, Milica
AU - Marković, Snežana D.
PY - 2019
UR - http://rimsi.imsi.bg.ac.rs/handle/123456789/1213
AB - 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(center dot-) 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(center dot-) concentration suggest that mitochondria are also involved in the apoptosis. T. chamaedrys methanol extract inhibits mRNA expression of CYP1A1, CYPIBI, 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.
PB - Elsevier Ireland Ltd, Clare
T2 - Journal of Ethnopharmacology
T1 - Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells
VL - 240
DO - 10.1016/j.jep.2019.111951
ER -
@article{
author = "Milutinović, Milena and Maksimović, Vuk and Cvetković, Danijela M. and Nikodijević, Danijela D. and Stanković, Milan and Pesic, Milica and Marković, Snežana D.",
year = "2019",
abstract = "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(center dot-) 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(center dot-) concentration suggest that mitochondria are also involved in the apoptosis. T. chamaedrys methanol extract inhibits mRNA expression of CYP1A1, CYPIBI, 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.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Journal of Ethnopharmacology",
title = "Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells",
volume = "240",
doi = "10.1016/j.jep.2019.111951"
}
Milutinović, M., Maksimović, V., Cvetković, D. M., Nikodijević, D. D., Stanković, M., Pesic, M.,& Marković, S. D.. (2019). Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells. in Journal of Ethnopharmacology
Elsevier Ireland Ltd, Clare., 240.
https://doi.org/10.1016/j.jep.2019.111951
Milutinović M, Maksimović V, Cvetković DM, Nikodijević DD, Stanković M, Pesic M, Marković SD. Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells. in Journal of Ethnopharmacology. 2019;240.
doi:10.1016/j.jep.2019.111951 .
Milutinović, Milena, Maksimović, Vuk, Cvetković, Danijela M., Nikodijević, Danijela D., Stanković, Milan, Pesic, Milica, Marković, Snežana D., "Potential of Teucrium chamaedrys L. to modulate apoptosis and biotransformation in colorectal carcinoma cells" in Journal of Ethnopharmacology, 240 (2019),
https://doi.org/10.1016/j.jep.2019.111951 . .
