The Molecular Mechanisms of Apoptosis Induced by Allium flavumL. and Synergistic Effects with New-Synthesized Pd(II) Complex on Colon Cancer Cells
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Milutinović, Milena
Stanković, Milan

Cvetković, Danijela
Maksimović, Vuk

Smit, Biljana

Pavlović, Radoslav
Marković, Snežana

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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 App...licationsIn 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.
Keywords:
Colon cancer / Allium flavum / HPLC / caffeic glycosides / superoxide anion radicalSource:
Journal of Food Biochemistry, 2015, 39, 3, 238-250Publisher:
- Wiley, Hoboken
Funding / projects:
- Preclinical investigation of bioactive substances (RS-41010)
- The membranes as sites of interaction between the intracellular and apoplastic environments: studies of the bioenergetics and signaling using biophysical and biochemical techniques. (RS-173040)
- Synthesis, modeling, physicochemical and biological properties of organic compounds and related metal complexes (RS-172016)
DOI: 10.1111/jfbc.12123
ISSN: 0145-8884
WoS: 000355981100004
Scopus: 2-s2.0-84930583036
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Institut za multidisciplinarna istraživanjaTY - 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 . .