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The combination of gamma ionizing radiation and 8-Cl-cAMP induces synergistic cell growth inhibition and induction of apoptosis in human prostate cancer cells
The antiproliferative and cytotoxic potential of the nucleotide analog 8-Cl-cAMP was tested in PC-3 and DU145 metastatic human prostate cancer cells. The drug was examined as the only therapeutic agent and in combination with ionizing irradiation (IR). Highly synergistic effects of IR and 8-Cl-cAMP were observed in both cell lines when examined by the MTT viability and BrdU proliferation assays. The combination of IR and 8-Cl-cAMP at clinically relevant doses exerted substantial growth inhibition. The combination of IR and 8-Cl-cAMP caused a significant disturbance in the distribution of cell cycle phases. Cell cycle arrest in the sub-G0/G1 phase predominated in both cell lines. The most striking observation was a significant increase in apoptotic PC-3 and DU145 cells. The DU145 cells were three times more sensitive to the combined treatment than PC-3 cells. The initial resistance to IR-induced apoptosis in these p53-deficient prostate cancer cell lines was overcome through an alternat...ive proapoptotic pathway induced by 8-Cl-cAMP. Considering the low effective doses of treatments, improved tumor eradication rates and minimal undesirable side effects, the combination of IR and 8-Cl-cAMP could be the therapy of choice in treating prostate cancer.
TY - JOUR
AU - Vučić, Vesna M.
AU - Niciforović, Ana
AU - Adžić, Miroslav
AU - Radojcić, Marija B.
AU - Ruždijić, Sabera
PY - 2008
UR - http://rimi.imi.bg.ac.rs/handle/123456789/191
AB - The antiproliferative and cytotoxic potential of the nucleotide analog 8-Cl-cAMP was tested in PC-3 and DU145 metastatic human prostate cancer cells. The drug was examined as the only therapeutic agent and in combination with ionizing irradiation (IR). Highly synergistic effects of IR and 8-Cl-cAMP were observed in both cell lines when examined by the MTT viability and BrdU proliferation assays. The combination of IR and 8-Cl-cAMP at clinically relevant doses exerted substantial growth inhibition. The combination of IR and 8-Cl-cAMP caused a significant disturbance in the distribution of cell cycle phases. Cell cycle arrest in the sub-G0/G1 phase predominated in both cell lines. The most striking observation was a significant increase in apoptotic PC-3 and DU145 cells. The DU145 cells were three times more sensitive to the combined treatment than PC-3 cells. The initial resistance to IR-induced apoptosis in these p53-deficient prostate cancer cell lines was overcome through an alternative proapoptotic pathway induced by 8-Cl-cAMP. Considering the low effective doses of treatments, improved tumor eradication rates and minimal undesirable side effects, the combination of IR and 8-Cl-cAMP could be the therapy of choice in treating prostate cancer.
PB - Springer, Dordrecht
T2 - Investigational New Drugs
T1 - The combination of gamma ionizing radiation and 8-Cl-cAMP induces synergistic cell growth inhibition and induction of apoptosis in human prostate cancer cells
EP - 317
IS - 4
SP - 309
VL - 26
DO - 10.1007/s10637-007-9101-4
UR - conv_1952
ER -
@article{
author = "Vučić, Vesna M. and Niciforović, Ana and Adžić, Miroslav and Radojcić, Marija B. and Ruždijić, Sabera",
year = "2008",
abstract = "The antiproliferative and cytotoxic potential of the nucleotide analog 8-Cl-cAMP was tested in PC-3 and DU145 metastatic human prostate cancer cells. The drug was examined as the only therapeutic agent and in combination with ionizing irradiation (IR). Highly synergistic effects of IR and 8-Cl-cAMP were observed in both cell lines when examined by the MTT viability and BrdU proliferation assays. The combination of IR and 8-Cl-cAMP at clinically relevant doses exerted substantial growth inhibition. The combination of IR and 8-Cl-cAMP caused a significant disturbance in the distribution of cell cycle phases. Cell cycle arrest in the sub-G0/G1 phase predominated in both cell lines. The most striking observation was a significant increase in apoptotic PC-3 and DU145 cells. The DU145 cells were three times more sensitive to the combined treatment than PC-3 cells. The initial resistance to IR-induced apoptosis in these p53-deficient prostate cancer cell lines was overcome through an alternative proapoptotic pathway induced by 8-Cl-cAMP. Considering the low effective doses of treatments, improved tumor eradication rates and minimal undesirable side effects, the combination of IR and 8-Cl-cAMP could be the therapy of choice in treating prostate cancer.",
publisher = "Springer, Dordrecht",
journal = "Investigational New Drugs",
title = "The combination of gamma ionizing radiation and 8-Cl-cAMP induces synergistic cell growth inhibition and induction of apoptosis in human prostate cancer cells",
pages = "317-309",
number = "4",
volume = "26",
doi = "10.1007/s10637-007-9101-4",
url = "conv_1952"
}
Vučić, V. M., Niciforović, A., Adžić, M., Radojcić, M. B.,& Ruždijić, S.. (2008). The combination of gamma ionizing radiation and 8-Cl-cAMP induces synergistic cell growth inhibition and induction of apoptosis in human prostate cancer cells. in Investigational New Drugs
Springer, Dordrecht., 26(4), 309-317.
https://doi.org/10.1007/s10637-007-9101-4
conv_1952
Vučić VM, Niciforović A, Adžić M, Radojcić MB, Ruždijić S. The combination of gamma ionizing radiation and 8-Cl-cAMP induces synergistic cell growth inhibition and induction of apoptosis in human prostate cancer cells. in Investigational New Drugs. 2008;26(4):309-317.
doi:10.1007/s10637-007-9101-4
conv_1952 .
Vučić, Vesna M., Niciforović, Ana, Adžić, Miroslav, Radojcić, Marija B., Ruždijić, Sabera, "The combination of gamma ionizing radiation and 8-Cl-cAMP induces synergistic cell growth inhibition and induction of apoptosis in human prostate cancer cells" in Investigational New Drugs, 26, no. 4 (2008):309-317,
https://doi.org/10.1007/s10637-007-9101-4 .,
conv_1952 .
