Multiple antimelanoma potential of dry olive leaf extract
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2011
Authors
Mijatović, Sanja A.Timotijević, Gordana
Miljković, Djordje M.
Radović, Julijana M.
Maksimović-Ivanić, Danijela
Dekanski, Dragana P.
Stošić-Grujičić, Stanislava
Article (Published version)
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Various constituents of the olive tree (Olea europaea) have been traditionally used in the treatment of infection, inflammation, prevention of chronic diseases, cardiovascular disorders and cancer. The anticancer potential of dry olive leaf extract (DOLE) represents the net effect of multilevel interactions between different biologically active compounds from the extract, cancer cells and conventional therapy. In this context, it was of primary interest to evaluate the influence of DOLE on progression of the highly malignant, immuno-and chemoresistant type of skin cancer-melanoma. DOLE significantly inhibited proliferation and subsequently restricted clonogenicity of the B16 mouse melanoma cell line in vitro. Moreover, late phase tumor treatment with DOLE significantly reduced tumor volume in a syngeneic strain of mice. DOLE-treated B16 cells were blocked in the G(0)/G(1) phase of the cell cycle, underwent early apoptosis and died by late necrosis. At the molecular level, the dying pro...cess started as caspase dependent, but finalized as caspase independent. In concordance, overexpression of antiapoptotic members of the Bcl-2 family, Bcl-2 and Bcl-XL, and diminished expression of their natural antagonists, Bim and p53, were observed. Despite molecular suppression of the proapoptotic process, DOLE successfully promoted cell death mainly through disruption of cell membrane integrity and late caspase-independent fragmentation of genetic material. Taken together, the results of this study indicate that DOLE possesses strong antimelanoma potential. When DOLE was applied in combination with different chemotherapeutics, various outcomes, including synergy and antagonism, were observed. This requires caution in the use of the extract as a supplementary antitumor therapeutic.
Keywords:
olive leaf extract / necrosis / melanoma / cell death / apoptosisSource:
International Journal of Cancer, 2011, 128, 8, 1955-1965Publisher:
- Wiley, Hoboken
Funding / projects:
- Fiziološka i farmakološka modulacija imunoinflamatornih i malignih bolesti (RS-MESTD-MPN2006-2010-143029)
DOI: 10.1002/ijc.25526
ISSN: 0020-7136
PubMed: 20568104
WoS: 000288037400022
Scopus: 2-s2.0-79951971044
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Mijatović, Sanja A. AU - Timotijević, Gordana AU - Miljković, Djordje M. AU - Radović, Julijana M. AU - Maksimović-Ivanić, Danijela AU - Dekanski, Dragana P. AU - Stošić-Grujičić, Stanislava PY - 2011 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/486 AB - Various constituents of the olive tree (Olea europaea) have been traditionally used in the treatment of infection, inflammation, prevention of chronic diseases, cardiovascular disorders and cancer. The anticancer potential of dry olive leaf extract (DOLE) represents the net effect of multilevel interactions between different biologically active compounds from the extract, cancer cells and conventional therapy. In this context, it was of primary interest to evaluate the influence of DOLE on progression of the highly malignant, immuno-and chemoresistant type of skin cancer-melanoma. DOLE significantly inhibited proliferation and subsequently restricted clonogenicity of the B16 mouse melanoma cell line in vitro. Moreover, late phase tumor treatment with DOLE significantly reduced tumor volume in a syngeneic strain of mice. DOLE-treated B16 cells were blocked in the G(0)/G(1) phase of the cell cycle, underwent early apoptosis and died by late necrosis. At the molecular level, the dying process started as caspase dependent, but finalized as caspase independent. In concordance, overexpression of antiapoptotic members of the Bcl-2 family, Bcl-2 and Bcl-XL, and diminished expression of their natural antagonists, Bim and p53, were observed. Despite molecular suppression of the proapoptotic process, DOLE successfully promoted cell death mainly through disruption of cell membrane integrity and late caspase-independent fragmentation of genetic material. Taken together, the results of this study indicate that DOLE possesses strong antimelanoma potential. When DOLE was applied in combination with different chemotherapeutics, various outcomes, including synergy and antagonism, were observed. This requires caution in the use of the extract as a supplementary antitumor therapeutic. PB - Wiley, Hoboken T2 - International Journal of Cancer T1 - Multiple antimelanoma potential of dry olive leaf extract EP - 1965 IS - 8 SP - 1955 VL - 128 DO - 10.1002/ijc.25526 ER -
@article{ author = "Mijatović, Sanja A. and Timotijević, Gordana and Miljković, Djordje M. and Radović, Julijana M. and Maksimović-Ivanić, Danijela and Dekanski, Dragana P. and Stošić-Grujičić, Stanislava", year = "2011", abstract = "Various constituents of the olive tree (Olea europaea) have been traditionally used in the treatment of infection, inflammation, prevention of chronic diseases, cardiovascular disorders and cancer. The anticancer potential of dry olive leaf extract (DOLE) represents the net effect of multilevel interactions between different biologically active compounds from the extract, cancer cells and conventional therapy. In this context, it was of primary interest to evaluate the influence of DOLE on progression of the highly malignant, immuno-and chemoresistant type of skin cancer-melanoma. DOLE significantly inhibited proliferation and subsequently restricted clonogenicity of the B16 mouse melanoma cell line in vitro. Moreover, late phase tumor treatment with DOLE significantly reduced tumor volume in a syngeneic strain of mice. DOLE-treated B16 cells were blocked in the G(0)/G(1) phase of the cell cycle, underwent early apoptosis and died by late necrosis. At the molecular level, the dying process started as caspase dependent, but finalized as caspase independent. In concordance, overexpression of antiapoptotic members of the Bcl-2 family, Bcl-2 and Bcl-XL, and diminished expression of their natural antagonists, Bim and p53, were observed. Despite molecular suppression of the proapoptotic process, DOLE successfully promoted cell death mainly through disruption of cell membrane integrity and late caspase-independent fragmentation of genetic material. Taken together, the results of this study indicate that DOLE possesses strong antimelanoma potential. When DOLE was applied in combination with different chemotherapeutics, various outcomes, including synergy and antagonism, were observed. This requires caution in the use of the extract as a supplementary antitumor therapeutic.", publisher = "Wiley, Hoboken", journal = "International Journal of Cancer", title = "Multiple antimelanoma potential of dry olive leaf extract", pages = "1965-1955", number = "8", volume = "128", doi = "10.1002/ijc.25526" }
Mijatović, S. A., Timotijević, G., Miljković, D. M., Radović, J. M., Maksimović-Ivanić, D., Dekanski, D. P.,& Stošić-Grujičić, S.. (2011). Multiple antimelanoma potential of dry olive leaf extract. in International Journal of Cancer Wiley, Hoboken., 128(8), 1955-1965. https://doi.org/10.1002/ijc.25526
Mijatović SA, Timotijević G, Miljković DM, Radović JM, Maksimović-Ivanić D, Dekanski DP, Stošić-Grujičić S. Multiple antimelanoma potential of dry olive leaf extract. in International Journal of Cancer. 2011;128(8):1955-1965. doi:10.1002/ijc.25526 .
Mijatović, Sanja A., Timotijević, Gordana, Miljković, Djordje M., Radović, Julijana M., Maksimović-Ivanić, Danijela, Dekanski, Dragana P., Stošić-Grujičić, Stanislava, "Multiple antimelanoma potential of dry olive leaf extract" in International Journal of Cancer, 128, no. 8 (2011):1955-1965, https://doi.org/10.1002/ijc.25526 . .