Abstract
Anguidine, a protein synthesis inhibitor, has been shown to induce a reversible cell cycle arrest in exponentially growing Chinese hamster ovary cells. The effect of pretreatment with anguidine on the cytotoxicity of subsequently administered various chemotherapeutic agents, hyperthermia, and radiation was investigated. We found that anguidine greatly potentiated the cytotoxic activity of cis-dichlorodiammineplatinum(II) and melphalan by abolishing the initial shoulder and steeperilng the subsequent exponential portion of the survival curves. Bleomycin-induced cell kill was also potentiated by anguidine pretreatment but to a lesser extent. However, anguidine pretreatment did not substantially alter radiation cytotoxicity. In contrast, anguidine markedly reduced the lethal effect of hydroxyurea, 5-fluorouracil, and hyperthermia, three modalities with S-phase activity. To investigate whether both anguidine-induced potentiation and protection of cells by different antitumor agents were due to its induction of complete suspension of cycle traverse, experiments were also conducted with plateau-phase cultures. Whereas anguidine potentiated cis-dichlorodiammineplatinum(II) cytotoxicity in an identical fashion as noted in exponentially growing cells, its protective effect against lethal damage from Adriamycin was absent. Thus, it appears that the two opposite effects of anguidine modification of cell kill by cytotoxic agents (protection and potentiation) come about by two different mechanisms, with cell cycle arrest underlying cytoprotection and the mechanism of synergistic toxicity remaining obscure.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3070-3073 |
| Number of pages | 4 |
| Journal | Cancer Research |
| Volume | 43 |
| Issue number | 7 |
| State | Published - Jul 1 1983 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Potentiation of dna-reactive antineoplastic agents and protection against s-phase-specific agents by anguidine in chinese hamster ovary cells. / Hromas, Robert A; Barlogie, Barthel; Swartzendruber, Douglas; Drewinko, Benjamin.
In: Cancer Research, Vol. 43, No. 7, 01.07.1983, p. 3070-3073.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Potentiation of dna-reactive antineoplastic agents and protection against s-phase-specific agents by anguidine in chinese hamster ovary cells
AU - Hromas, Robert A
AU - Barlogie, Barthel
AU - Swartzendruber, Douglas
AU - Drewinko, Benjamin
PY - 1983/7/1
Y1 - 1983/7/1
N2 - Anguidine, a protein synthesis inhibitor, has been shown to induce a reversible cell cycle arrest in exponentially growing Chinese hamster ovary cells. The effect of pretreatment with anguidine on the cytotoxicity of subsequently administered various chemotherapeutic agents, hyperthermia, and radiation was investigated. We found that anguidine greatly potentiated the cytotoxic activity of cis-dichlorodiammineplatinum(II) and melphalan by abolishing the initial shoulder and steeperilng the subsequent exponential portion of the survival curves. Bleomycin-induced cell kill was also potentiated by anguidine pretreatment but to a lesser extent. However, anguidine pretreatment did not substantially alter radiation cytotoxicity. In contrast, anguidine markedly reduced the lethal effect of hydroxyurea, 5-fluorouracil, and hyperthermia, three modalities with S-phase activity. To investigate whether both anguidine-induced potentiation and protection of cells by different antitumor agents were due to its induction of complete suspension of cycle traverse, experiments were also conducted with plateau-phase cultures. Whereas anguidine potentiated cis-dichlorodiammineplatinum(II) cytotoxicity in an identical fashion as noted in exponentially growing cells, its protective effect against lethal damage from Adriamycin was absent. Thus, it appears that the two opposite effects of anguidine modification of cell kill by cytotoxic agents (protection and potentiation) come about by two different mechanisms, with cell cycle arrest underlying cytoprotection and the mechanism of synergistic toxicity remaining obscure.
AB - Anguidine, a protein synthesis inhibitor, has been shown to induce a reversible cell cycle arrest in exponentially growing Chinese hamster ovary cells. The effect of pretreatment with anguidine on the cytotoxicity of subsequently administered various chemotherapeutic agents, hyperthermia, and radiation was investigated. We found that anguidine greatly potentiated the cytotoxic activity of cis-dichlorodiammineplatinum(II) and melphalan by abolishing the initial shoulder and steeperilng the subsequent exponential portion of the survival curves. Bleomycin-induced cell kill was also potentiated by anguidine pretreatment but to a lesser extent. However, anguidine pretreatment did not substantially alter radiation cytotoxicity. In contrast, anguidine markedly reduced the lethal effect of hydroxyurea, 5-fluorouracil, and hyperthermia, three modalities with S-phase activity. To investigate whether both anguidine-induced potentiation and protection of cells by different antitumor agents were due to its induction of complete suspension of cycle traverse, experiments were also conducted with plateau-phase cultures. Whereas anguidine potentiated cis-dichlorodiammineplatinum(II) cytotoxicity in an identical fashion as noted in exponentially growing cells, its protective effect against lethal damage from Adriamycin was absent. Thus, it appears that the two opposite effects of anguidine modification of cell kill by cytotoxic agents (protection and potentiation) come about by two different mechanisms, with cell cycle arrest underlying cytoprotection and the mechanism of synergistic toxicity remaining obscure.
UR - http://www.scopus.com/inward/record.url?scp=0020595543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0020595543&partnerID=8YFLogxK
M3 - Article
VL - 43
SP - 3070
EP - 3073
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 7
ER -