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  - Pesic, Milica
AU  - Podolski-Renic, Ana
AU  - Stojković, Sonja
AU  - Matović, Branko
AU  - Zmejkoski, Danica
AU  - Kojić, Vesna
AU  - Bogdanović, Gordana
AU  - Pavicević, Aleksandra
AU  - Mojović, Miloš
AU  - Savić, Aleksandar G
AU  - Milenković, Ivana
AU  - Kalauzi, Aleksandar
AU  - Radotić, Ksenija
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/931
AB  - Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-Biological Interactions
T1  - Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity
EP  - 93
SP  - 85
VL  - 232
DO  - 10.1016/j.cbi.2015.03.013
ER  - 

@article{
author = "Pesic, Milica and Podolski-Renic, Ana and Stojković, Sonja and Matović, Branko and Zmejkoski, Danica and Kojić, Vesna and Bogdanović, Gordana and Pavicević, Aleksandra and Mojović, Miloš and Savić, Aleksandar G and Milenković, Ivana and Kalauzi, Aleksandar and Radotić, Ksenija",
year = "2015",
abstract = "Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce3+ and O2- vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 mu M. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity",
pages = "93-85",
volume = "232",
doi = "10.1016/j.cbi.2015.03.013"
}

Pesic, M., Podolski-Renic, A., Stojković, S., Matović, B., Zmejkoski, D., Kojić, V., Bogdanović, G., Pavicević, A., Mojović, M., Savić, A. G., Milenković, I., Kalauzi, A.,& Radotić, K.. (2015). Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 232, 85-93.
https://doi.org/10.1016/j.cbi.2015.03.013

Pesic M, Podolski-Renic A, Stojković S, Matović B, Zmejkoski D, Kojić V, Bogdanović G, Pavicević A, Mojović M, Savić AG, Milenković I, Kalauzi A, Radotić K. Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. in Chemico-Biological Interactions. 2015;232:85-93.
doi:10.1016/j.cbi.2015.03.013 .

Pesic, Milica, Podolski-Renic, Ana, Stojković, Sonja, Matović, Branko, Zmejkoski, Danica, Kojić, Vesna, Bogdanović, Gordana, Pavicević, Aleksandra, Mojović, Miloš, Savić, Aleksandar G, Milenković, Ivana, Kalauzi, Aleksandar, Radotić, Ksenija, "Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity" in Chemico-Biological Interactions, 232 (2015):85-93,
https://doi.org/10.1016/j.cbi.2015.03.013 . .