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 . .

TY  - JOUR
AU  - Milutinović, Milena
AU  - Stanković, Milan
AU  - Cvetković, Danijela
AU  - Maksimović, Vuk
AU  - Smit, Biljana
AU  - Pavlović, Radoslav
AU  - Marković, Snežana
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/870
AB  - Considering that induction of apoptosis is one of the main strategies in cancer therapy, the molecular mechanisms of cytotoxic effects of Allium flavumL. on colon cancer cell lines were investigated and applied in single and co-treatments with new-synthesized Pd(II) complex. The analysis of chemical composition identified caffeic acid glycosides as the most dominant phenolics in A.flavum extract. In all investigated extracts, A.flavum showed cytotoxic effects on colon cancer cells (IC50=1.64-84g/mL) but not on healthy cells. Combinations of plant extracts with Pd(II) complex caused lower IC50 values and better proapoptotic activity. Pd(II) complex induced high percentage of necrosis in a single treatment, but in the combination with plant extracts it had better proapoptotic and lower necrotic activity. Treatments and co-treatments induced higher O-2(-) production and influenced apoptosis biomarkers, leading to Fas protein overexpression and activation of caspases 8 and 9. Practical ApplicationsIn view of the achieved anticancer properties, insufficiently investigated Allium flavum L. is a promising candidate for developing new anticancer compounds and deserves further research and scientific validation. This study has great impact on investigation of new anticancer substances from natural source, focuses on the importance of using plants as the source of medicinal drugs, contributes to the development of the appropriate therapy and gives contribution in both scientific and practical means. Because of its synergistic actions with the newly synthesized chemical anticancer agent and ability to reduce side effects (thus reducing necrotic activity of Pd[II] complex), A.flavum can be used as a dietary food supplement or supplement to chemotherapy perhaps in combination with currently used chemotherapeutics or in some strategies in cancer therapy. This finding is also important from a nutritional point of view because this extracts contain significant amounts of bioactive constituents, which provide health benefits.
PB  - Wiley, Hoboken
T2  - Journal of Food Biochemistry
T1  - The Molecular Mechanisms of Apoptosis Induced by Allium flavumL. and Synergistic Effects with New-Synthesized Pd(II) Complex on Colon Cancer Cells
EP  - 250
IS  - 3
SP  - 238
VL  - 39
DO  - 10.1111/jfbc.12123
ER  - 

@article{
author = "Milutinović, Milena and Stanković, Milan and Cvetković, Danijela and Maksimović, Vuk and Smit, Biljana and Pavlović, Radoslav and Marković, Snežana",
year = "2015",
abstract = "Considering that induction of apoptosis is one of the main strategies in cancer therapy, the molecular mechanisms of cytotoxic effects of Allium flavumL. on colon cancer cell lines were investigated and applied in single and co-treatments with new-synthesized Pd(II) complex. The analysis of chemical composition identified caffeic acid glycosides as the most dominant phenolics in A.flavum extract. In all investigated extracts, A.flavum showed cytotoxic effects on colon cancer cells (IC50=1.64-84g/mL) but not on healthy cells. Combinations of plant extracts with Pd(II) complex caused lower IC50 values and better proapoptotic activity. Pd(II) complex induced high percentage of necrosis in a single treatment, but in the combination with plant extracts it had better proapoptotic and lower necrotic activity. Treatments and co-treatments induced higher O-2(-) production and influenced apoptosis biomarkers, leading to Fas protein overexpression and activation of caspases 8 and 9. Practical ApplicationsIn view of the achieved anticancer properties, insufficiently investigated Allium flavum L. is a promising candidate for developing new anticancer compounds and deserves further research and scientific validation. This study has great impact on investigation of new anticancer substances from natural source, focuses on the importance of using plants as the source of medicinal drugs, contributes to the development of the appropriate therapy and gives contribution in both scientific and practical means. Because of its synergistic actions with the newly synthesized chemical anticancer agent and ability to reduce side effects (thus reducing necrotic activity of Pd[II] complex), A.flavum can be used as a dietary food supplement or supplement to chemotherapy perhaps in combination with currently used chemotherapeutics or in some strategies in cancer therapy. This finding is also important from a nutritional point of view because this extracts contain significant amounts of bioactive constituents, which provide health benefits.",
publisher = "Wiley, Hoboken",
journal = "Journal of Food Biochemistry",
title = "The Molecular Mechanisms of Apoptosis Induced by Allium flavumL. and Synergistic Effects with New-Synthesized Pd(II) Complex on Colon Cancer Cells",
pages = "250-238",
number = "3",
volume = "39",
doi = "10.1111/jfbc.12123"
}

Milutinović, M., Stanković, M., Cvetković, D., Maksimović, V., Smit, B., Pavlović, R.,& Marković, S.. (2015). The Molecular Mechanisms of Apoptosis Induced by Allium flavumL. and Synergistic Effects with New-Synthesized Pd(II) Complex on Colon Cancer Cells. in Journal of Food Biochemistry
Wiley, Hoboken., 39(3), 238-250.
https://doi.org/10.1111/jfbc.12123

Milutinović M, Stanković M, Cvetković D, Maksimović V, Smit B, Pavlović R, Marković S. The Molecular Mechanisms of Apoptosis Induced by Allium flavumL. and Synergistic Effects with New-Synthesized Pd(II) Complex on Colon Cancer Cells. in Journal of Food Biochemistry. 2015;39(3):238-250.
doi:10.1111/jfbc.12123 .

Milutinović, Milena, Stanković, Milan, Cvetković, Danijela, Maksimović, Vuk, Smit, Biljana, Pavlović, Radoslav, Marković, Snežana, "The Molecular Mechanisms of Apoptosis Induced by Allium flavumL. and Synergistic Effects with New-Synthesized Pd(II) Complex on Colon Cancer Cells" in Journal of Food Biochemistry, 39, no. 3 (2015):238-250,
https://doi.org/10.1111/jfbc.12123 . .