Apoptosis and clonogenic cell death in PC3 human prostate cancer cells after treatment with gamma radiation and suramin

Sanjeewani T. Palayoor, Edward A. Bump, Beverly A. Teicher, C. Norman Coleman

Research output: Contribution to journalArticle

Abstract

Suramin is a novel cytostatic/cytotoxic agent that is currently undergoing clinical trials in the treatment of hormone- and chemo-refractory tumors. Its unusual mechanism of action and its activity against prostate cancer raise the possibility that it could be particularly suitable for combined-modality treatment of prostate cancer. PC3 human prostate cancer cells were used as an in vitro model to test the possible interaction between suramin and ionizing radiation. Treatment with γ radiation resulted in detachment of PC3 cells from the monolayer, and the detached cells exhibited internucleosomal DNA fragmentation characteristic of apoptosis. Low concentrations of suramin (50-100 μg/ml, 35-70 μM) increased spontaneous as well as radiation-enhanced apoptosis. However, suramin inhibited spontaneous and radiation-enhanced apoptosis at 300 μg/ml (210 μM), a concentration that is more commonly used in the clinic. At this concentration suramin inhibited DNA fragmentation induced by chemotherapeutic drugs as well. The effect of suramin on inhibition of DNA fragmentation was reversible if the suramin was removed 24 h after irradiation. Despite inhibition of radiation- induced apoptosis by 300 μg/ml suramin (from 5% to 2.9% at 48 h), clonogenic cell death was enhanced by the combination of suramin and radiation. The effects of radiation and suramin on clonogenic cell survival appeared to be additive by isobologram analysis at clinically relevant radiation doses. Continuous exposure to a lower concentration of suramin (100 μg/ml) during the clonogenic assay period was as effective in decreasing clonogenic survival as 48 h exposure to 300 μg/ml suramin in decreasing clonogenic survival. Our data indicate that, when used in combination with radiation, suramin may be effective at concentrations that are lower than those required for efficacy as a single agent.

Original languageEnglish (US)
Pages (from-to)105-114
Number of pages10
JournalRadiation Research
Volume148
Issue number2
DOIs
StatePublished - Aug 1997
Externally publishedYes

Fingerprint

suramin
Suramin
Gamma Rays
apoptosis
prostatic neoplasms
death
gamma radiation
cell death
Prostatic Neoplasms
Cell Death
cancer
gamma rays
Apoptosis
radiation
Radiation
fragmentation
deoxyribonucleic acid
DNA fragmentation
DNA Fragmentation
low concentrations

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Apoptosis and clonogenic cell death in PC3 human prostate cancer cells after treatment with gamma radiation and suramin. / Palayoor, Sanjeewani T.; Bump, Edward A.; Teicher, Beverly A.; Coleman, C. Norman.

In: Radiation Research, Vol. 148, No. 2, 08.1997, p. 105-114.

Research output: Contribution to journalArticle

Palayoor, Sanjeewani T. ; Bump, Edward A. ; Teicher, Beverly A. ; Coleman, C. Norman. / Apoptosis and clonogenic cell death in PC3 human prostate cancer cells after treatment with gamma radiation and suramin. In: Radiation Research. 1997 ; Vol. 148, No. 2. pp. 105-114.
@article{e092b9fc6adc45888a98f7c804704351,
title = "Apoptosis and clonogenic cell death in PC3 human prostate cancer cells after treatment with gamma radiation and suramin",
abstract = "Suramin is a novel cytostatic/cytotoxic agent that is currently undergoing clinical trials in the treatment of hormone- and chemo-refractory tumors. Its unusual mechanism of action and its activity against prostate cancer raise the possibility that it could be particularly suitable for combined-modality treatment of prostate cancer. PC3 human prostate cancer cells were used as an in vitro model to test the possible interaction between suramin and ionizing radiation. Treatment with γ radiation resulted in detachment of PC3 cells from the monolayer, and the detached cells exhibited internucleosomal DNA fragmentation characteristic of apoptosis. Low concentrations of suramin (50-100 μg/ml, 35-70 μM) increased spontaneous as well as radiation-enhanced apoptosis. However, suramin inhibited spontaneous and radiation-enhanced apoptosis at 300 μg/ml (210 μM), a concentration that is more commonly used in the clinic. At this concentration suramin inhibited DNA fragmentation induced by chemotherapeutic drugs as well. The effect of suramin on inhibition of DNA fragmentation was reversible if the suramin was removed 24 h after irradiation. Despite inhibition of radiation- induced apoptosis by 300 μg/ml suramin (from 5{\%} to 2.9{\%} at 48 h), clonogenic cell death was enhanced by the combination of suramin and radiation. The effects of radiation and suramin on clonogenic cell survival appeared to be additive by isobologram analysis at clinically relevant radiation doses. Continuous exposure to a lower concentration of suramin (100 μg/ml) during the clonogenic assay period was as effective in decreasing clonogenic survival as 48 h exposure to 300 μg/ml suramin in decreasing clonogenic survival. Our data indicate that, when used in combination with radiation, suramin may be effective at concentrations that are lower than those required for efficacy as a single agent.",
author = "Palayoor, {Sanjeewani T.} and Bump, {Edward A.} and Teicher, {Beverly A.} and Coleman, {C. Norman}",
year = "1997",
month = "8",
doi = "10.2307/3579566",
language = "English (US)",
volume = "148",
pages = "105--114",
journal = "Radiation Research",
issn = "0033-7587",
publisher = "Radiation Research Society",
number = "2",

}

TY - JOUR

T1 - Apoptosis and clonogenic cell death in PC3 human prostate cancer cells after treatment with gamma radiation and suramin

AU - Palayoor, Sanjeewani T.

AU - Bump, Edward A.

AU - Teicher, Beverly A.

AU - Coleman, C. Norman

PY - 1997/8

Y1 - 1997/8

N2 - Suramin is a novel cytostatic/cytotoxic agent that is currently undergoing clinical trials in the treatment of hormone- and chemo-refractory tumors. Its unusual mechanism of action and its activity against prostate cancer raise the possibility that it could be particularly suitable for combined-modality treatment of prostate cancer. PC3 human prostate cancer cells were used as an in vitro model to test the possible interaction between suramin and ionizing radiation. Treatment with γ radiation resulted in detachment of PC3 cells from the monolayer, and the detached cells exhibited internucleosomal DNA fragmentation characteristic of apoptosis. Low concentrations of suramin (50-100 μg/ml, 35-70 μM) increased spontaneous as well as radiation-enhanced apoptosis. However, suramin inhibited spontaneous and radiation-enhanced apoptosis at 300 μg/ml (210 μM), a concentration that is more commonly used in the clinic. At this concentration suramin inhibited DNA fragmentation induced by chemotherapeutic drugs as well. The effect of suramin on inhibition of DNA fragmentation was reversible if the suramin was removed 24 h after irradiation. Despite inhibition of radiation- induced apoptosis by 300 μg/ml suramin (from 5% to 2.9% at 48 h), clonogenic cell death was enhanced by the combination of suramin and radiation. The effects of radiation and suramin on clonogenic cell survival appeared to be additive by isobologram analysis at clinically relevant radiation doses. Continuous exposure to a lower concentration of suramin (100 μg/ml) during the clonogenic assay period was as effective in decreasing clonogenic survival as 48 h exposure to 300 μg/ml suramin in decreasing clonogenic survival. Our data indicate that, when used in combination with radiation, suramin may be effective at concentrations that are lower than those required for efficacy as a single agent.

AB - Suramin is a novel cytostatic/cytotoxic agent that is currently undergoing clinical trials in the treatment of hormone- and chemo-refractory tumors. Its unusual mechanism of action and its activity against prostate cancer raise the possibility that it could be particularly suitable for combined-modality treatment of prostate cancer. PC3 human prostate cancer cells were used as an in vitro model to test the possible interaction between suramin and ionizing radiation. Treatment with γ radiation resulted in detachment of PC3 cells from the monolayer, and the detached cells exhibited internucleosomal DNA fragmentation characteristic of apoptosis. Low concentrations of suramin (50-100 μg/ml, 35-70 μM) increased spontaneous as well as radiation-enhanced apoptosis. However, suramin inhibited spontaneous and radiation-enhanced apoptosis at 300 μg/ml (210 μM), a concentration that is more commonly used in the clinic. At this concentration suramin inhibited DNA fragmentation induced by chemotherapeutic drugs as well. The effect of suramin on inhibition of DNA fragmentation was reversible if the suramin was removed 24 h after irradiation. Despite inhibition of radiation- induced apoptosis by 300 μg/ml suramin (from 5% to 2.9% at 48 h), clonogenic cell death was enhanced by the combination of suramin and radiation. The effects of radiation and suramin on clonogenic cell survival appeared to be additive by isobologram analysis at clinically relevant radiation doses. Continuous exposure to a lower concentration of suramin (100 μg/ml) during the clonogenic assay period was as effective in decreasing clonogenic survival as 48 h exposure to 300 μg/ml suramin in decreasing clonogenic survival. Our data indicate that, when used in combination with radiation, suramin may be effective at concentrations that are lower than those required for efficacy as a single agent.

UR - http://www.scopus.com/inward/record.url?scp=0030807492&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030807492&partnerID=8YFLogxK

U2 - 10.2307/3579566

DO - 10.2307/3579566

M3 - Article

C2 - 9254728

AN - SCOPUS:0030807492

VL - 148

SP - 105

EP - 114

JO - Radiation Research

JF - Radiation Research

SN - 0033-7587

IS - 2

ER -