TY  - JOUR
AU  - Mojic, Marija
AU  - Bogdanović Pristov, Jelena
AU  - Maksimović-Ivanić, Danijela
AU  - Jones, David R
AU  - Stanić, Marina
AU  - Mijatović, Sanja
AU  - Spasojević, Ivan
PY  - 2014
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/821
AB  - In vitro studies have shown that hydrogen peroxide (H2O2) produced by high-concentration ascorbate and cell culture medium iron efficiently kills cancer cells. This provided the rationale for clinical trials of high-dose intravenous ascorbate-based treatment for cancer. A drawback in all the in vitro studies was their failure to take into account the in vivo concentration of iron to supplement cell culture media which are characterized by low iron content. Here we showed, using two prostate cancer cell lines (LNCaP and PC-3) and primary astrocytes, that the anticancer/cytotoxic effects of ascorbate are completely abolished by iron at physiological concentrations in cell culture medium and human plasma. A detailed examination of mechanisms showed that iron at physiological concentrations promotes both production and decomposition of H2O2. The latter is mediated by Fenton reaction and prevents H2O2 accumulation. The hydroxyl radical, which is produced in the Fenton reaction, is buffered by extracellular proteins, and could not affect intracellular targets like H2O2. These findings show that anticancer effects of ascorbate have been significantly overestimated in previous in vitro studies, and that common cell culture media might be unsuitable for redox research.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study
VL  - 4
DO  - 10.1038/srep05955
ER  - 

@article{
author = "Mojic, Marija and Bogdanović Pristov, Jelena and Maksimović-Ivanić, Danijela and Jones, David R and Stanić, Marina and Mijatović, Sanja and Spasojević, Ivan",
year = "2014",
abstract = "In vitro studies have shown that hydrogen peroxide (H2O2) produced by high-concentration ascorbate and cell culture medium iron efficiently kills cancer cells. This provided the rationale for clinical trials of high-dose intravenous ascorbate-based treatment for cancer. A drawback in all the in vitro studies was their failure to take into account the in vivo concentration of iron to supplement cell culture media which are characterized by low iron content. Here we showed, using two prostate cancer cell lines (LNCaP and PC-3) and primary astrocytes, that the anticancer/cytotoxic effects of ascorbate are completely abolished by iron at physiological concentrations in cell culture medium and human plasma. A detailed examination of mechanisms showed that iron at physiological concentrations promotes both production and decomposition of H2O2. The latter is mediated by Fenton reaction and prevents H2O2 accumulation. The hydroxyl radical, which is produced in the Fenton reaction, is buffered by extracellular proteins, and could not affect intracellular targets like H2O2. These findings show that anticancer effects of ascorbate have been significantly overestimated in previous in vitro studies, and that common cell culture media might be unsuitable for redox research.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study",
volume = "4",
doi = "10.1038/srep05955"
}

Mojic, M., Bogdanović Pristov, J., Maksimović-Ivanić, D., Jones, D. R., Stanić, M., Mijatović, S.,& Spasojević, I.. (2014). Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study. in Scientific Reports
Nature Publishing Group, London., 4.
https://doi.org/10.1038/srep05955

Mojic M, Bogdanović Pristov J, Maksimović-Ivanić D, Jones DR, Stanić M, Mijatović S, Spasojević I. Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study. in Scientific Reports. 2014;4.
doi:10.1038/srep05955 .

Mojic, Marija, Bogdanović Pristov, Jelena, Maksimović-Ivanić, Danijela, Jones, David R, Stanić, Marina, Mijatović, Sanja, Spasojević, Ivan, "Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study" in Scientific Reports, 4 (2014),
https://doi.org/10.1038/srep05955 . .

TY  - JOUR
AU  - Ajdzanović, Vladimir Z
AU  - Mojic, Marija
AU  - Maksimović-Ivanić, Danijela
AU  - Bulatović, Mirna Z
AU  - Mijatović, Sanja
AU  - Milošević, Verica Lj.
AU  - Spasojević, Ivan
PY  - 2013
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/729
AB  - Soy isoflavones represent hopeful unconventional remedies in the therapy of prostate cancer. The aim of our study was to determine the effects of genistein and daidzein on the parameters that reflect metastatic potential, membrane fluidity, invasiveness and dynamic phenotype in Matrigel of LNCaP and PC-3 prostate cancer cells. Cell viability tests, using a wide range of concentrations of soy isoflavones (6-75 mu g/ml for 72 h), were conducted to determine their IC50 concentrations. Electron paramagnetic resonance investigations of prostate cancer cell membrane fluidity were performed at IC50 concentrations of genistein and daidzein (12.5 and 25 mu g/ml, respectively, for 10 min). Genistein provoked significant increases in the membrane order parameter (which is reciprocally proportional to membrane fluidity) of 0.722 +/- A 0.006 (LNCaP), 0.753 +/- A 0.010 (LNCaP + genistein), 0.723 +/- A 0.007 (PC-3) and 0.741 +/- A 0.004 (PC-3 + genistein); however, no such effects were observed for daidzein. While both genistein and daidzein reduced the proliferation of prostate cancer cells at their respective IC50 concentrations, during the 72 h of incubation only genistein provoked effects on the dynamic phenotype and decreased invasiveness. The effect was more evident in PC-3 cells compared to LNCaP cells. Our results imply that (1) invasive activity is at least partially dependent on membrane fluidity, (2) genistein may exert its antimetastatic effects by changing the mechanical properties of prostate cancer cells and (3) daidzein should be applied at higher concentrations than genistein in order to achieve pharmacological effects.
PB  - Springer, New York
T2  - Journal of Membrane Biology
T1  - Membrane Fluidity, Invasiveness and Dynamic Phenotype of Metastatic Prostate Cancer Cells after Treatment with Soy Isoflavones
EP  - 314
IS  - 4
SP  - 307
VL  - 246
DO  - 10.1007/s00232-013-9531-1
ER  - 

@article{
author = "Ajdzanović, Vladimir Z and Mojic, Marija and Maksimović-Ivanić, Danijela and Bulatović, Mirna Z and Mijatović, Sanja and Milošević, Verica Lj. and Spasojević, Ivan",
year = "2013",
abstract = "Soy isoflavones represent hopeful unconventional remedies in the therapy of prostate cancer. The aim of our study was to determine the effects of genistein and daidzein on the parameters that reflect metastatic potential, membrane fluidity, invasiveness and dynamic phenotype in Matrigel of LNCaP and PC-3 prostate cancer cells. Cell viability tests, using a wide range of concentrations of soy isoflavones (6-75 mu g/ml for 72 h), were conducted to determine their IC50 concentrations. Electron paramagnetic resonance investigations of prostate cancer cell membrane fluidity were performed at IC50 concentrations of genistein and daidzein (12.5 and 25 mu g/ml, respectively, for 10 min). Genistein provoked significant increases in the membrane order parameter (which is reciprocally proportional to membrane fluidity) of 0.722 +/- A 0.006 (LNCaP), 0.753 +/- A 0.010 (LNCaP + genistein), 0.723 +/- A 0.007 (PC-3) and 0.741 +/- A 0.004 (PC-3 + genistein); however, no such effects were observed for daidzein. While both genistein and daidzein reduced the proliferation of prostate cancer cells at their respective IC50 concentrations, during the 72 h of incubation only genistein provoked effects on the dynamic phenotype and decreased invasiveness. The effect was more evident in PC-3 cells compared to LNCaP cells. Our results imply that (1) invasive activity is at least partially dependent on membrane fluidity, (2) genistein may exert its antimetastatic effects by changing the mechanical properties of prostate cancer cells and (3) daidzein should be applied at higher concentrations than genistein in order to achieve pharmacological effects.",
publisher = "Springer, New York",
journal = "Journal of Membrane Biology",
title = "Membrane Fluidity, Invasiveness and Dynamic Phenotype of Metastatic Prostate Cancer Cells after Treatment with Soy Isoflavones",
pages = "314-307",
number = "4",
volume = "246",
doi = "10.1007/s00232-013-9531-1"
}

Ajdzanović, V. Z., Mojic, M., Maksimović-Ivanić, D., Bulatović, M. Z., Mijatović, S., Milošević, V. Lj.,& Spasojević, I.. (2013). Membrane Fluidity, Invasiveness and Dynamic Phenotype of Metastatic Prostate Cancer Cells after Treatment with Soy Isoflavones. in Journal of Membrane Biology
Springer, New York., 246(4), 307-314.
https://doi.org/10.1007/s00232-013-9531-1

Ajdzanović VZ, Mojic M, Maksimović-Ivanić D, Bulatović MZ, Mijatović S, Milošević VL, Spasojević I. Membrane Fluidity, Invasiveness and Dynamic Phenotype of Metastatic Prostate Cancer Cells after Treatment with Soy Isoflavones. in Journal of Membrane Biology. 2013;246(4):307-314.
doi:10.1007/s00232-013-9531-1 .

Ajdzanović, Vladimir Z, Mojic, Marija, Maksimović-Ivanić, Danijela, Bulatović, Mirna Z, Mijatović, Sanja, Milošević, Verica Lj., Spasojević, Ivan, "Membrane Fluidity, Invasiveness and Dynamic Phenotype of Metastatic Prostate Cancer Cells after Treatment with Soy Isoflavones" in Journal of Membrane Biology, 246, no. 4 (2013):307-314,
https://doi.org/10.1007/s00232-013-9531-1 . .