Sensitivity to camptothecin of human breast carcinoma and normal endothelial cells

Jones, Christopher; Clements, Mark K.; Wasi, Safia; Daoud, Sayed S.

doi:10.1007/s002800050690

Cited by 33 publications

(20 citation statements)

References 20 publications

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“…Camptothecin also shows close toxicity to both KB cells (IC 50 = 65 nmol/l) and IMR90 cells (IC 50 = 100 nmol/l). The IC 50 values from our pilot study are similar to those in the literature reports [23][24][25]. However, bortezomib inhibited the cell proliferation, with IC 50 levels of 1.5 and 100 nmol/l for KB and IMR90, respectively.…”

Section: Anticancer Study Of Individual Drugssupporting

confidence: 88%

Optimized combinations of bortezomib, camptothecin, and doxorubicin show increased efficacy and reduced toxicity in treating oral cancer

Matsuo

Lin

et al. 2015

Anti-Cancer Drugs

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Oral cancer continues to be a major cause of morbidity and mortality worldwide. Treatment of oral cancer with combinatorial drugs is increasingly being performed as drugs with different molecular targets often exert synergistic effects, thereby enhancing treatment efficacy. Current combinatorial drug regimens often combine the tolerable dosages of individual drugs. However, the optimized ratio of a drug combination and sequence of drug administration could contribute toward the synergy, leading to increased efficacy and reduced dosages. This report aims to study the possible synergistic effects of three anticancer drugs, a proteasome inhibitor, bortezomib, a topoisomerase I inhibitor, Camptothecin, and a DNA intercalation drug, Doxorubicin, when used in combination for treating oral cancer. To rapidly optimize the three-drug regimen with minimal experimental efforts, a Feedback System Control optimization technique, a recent platform technique developed particularly for drug combination screening, was applied. The optimized regimen showed a therapeutic window (death rate difference between cancer cells and normal cells) close to 100%. This is the first report on the use of a combination of bortezomib, Camptothecin, and Doxorubicin in the treatment of oral cancer. Our results indicate that to have the most synergistic anticancer effect, the drugs in the optimized regimen should be dosage specific and ratio specific. Furthermore, the sequence of drug administration plays a vital role in ensuring that the combination is effective. The optimized regimen reported here has the potential to considerably increase the cure rate of oral cancer and reduce the toxicity of chemotherapy.

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Section: Anticancer Study Of Individual Drugssupporting

confidence: 88%

Optimized combinations of bortezomib, camptothecin, and doxorubicin show increased efficacy and reduced toxicity in treating oral cancer

Matsuo

Lin

et al. 2015

Anti-Cancer Drugs

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“…Ellipticine and camptothecin were previously tested in other cell lines with the use of other methodologies. For these studies, CC 50 values of 0.3 to 3 M for ellipticine (13,42) and 7 to 330 nM for camptothecin (7,21) were reported. Although there are variations in toxicity among the cell lines and the methods chosen in these studies, these CC 50 values basically agree with the results reported in this study, pointing out the validity of the trypan blue exclusion method employed in the current study to evaluate cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Potent Antiviral Activity of Topoisomerase I and II Inhibitors against Kaposi's Sarcoma-Associated Herpesvirus

González-Molleda

Yan

Yuan

2012

Antimicrob Agents Chemother

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. To assess the importance of these topoisomerases in viral lytic replication, shRNA-mediated gene silencing was used. Depletion of Topo I and II severely inhibited viral lytic DNA replication as well as virion production, suggesting essential roles of these cellular proteins in viral DNA replication. The discovery of Topo I and II as enzymes indispensable for KSHV DNA replication raises a possibility that these cellular proteins could be new targets of therapeutic approaches to halt KSHV replication and treat KSHV-associated diseases. In this report, we examined one Topo I inhibitor and several Topo II inhibitors (inclusive of Topo II poison and catalytic inhibitors) as potential therapeutic agents for blocking KSHV replication. The Topo II catalytic inhibitors in general exhibited marked inhibition on KSHV replication and minimal cytotoxicity. In particular, novobiocin, with the best selectivity index (SI ‫؍‬ 31.62) among the inhibitors tested in this study, is effective in inhibiting KSHV DNA replication and virion production but shows little adverse effect on cell proliferation and cycle progression in its therapeutic concentration, suggesting its potential to become an effective and safe drug for the treatment of human diseases associated with KSHV infection.

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“…Studies by our laboratories and others, for example, showed that p53 mutations in human tumor cells were correlated with decreased sensitivity to DNA damaging agents [3][4][5][6]. Hence an improved understanding of the relationship between p53 and chemosensitivity may lay the groundwork for new cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

Proteomics Characterization of the Molecular Mechanisms of Mutant P53 Reactivation with PRIMA-1 in Breast Cancer Cells

Daoud¹

2006

Self Cite

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY) PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERWashington State University Pullman, Washington 99164-1025 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 0riginal contains colored plates: ALL DTIC reproductions will be in black and white. ABSTRACTThe main purpose of the study is to identify novel protein-protein interactions in various locations of cells to establish the molecular mechanisms of mutant p53 reactivation with PRIMA-1 in breast cancer cells. To achieve this goal, co-immunoprecipitation/mass spectrometry approaches are used to search for novel proteins that interact with p53 in the cytoplasmic and nuclear fractions of cells. The identity of interacting proteins are validated and confirmed by immunoblot analyses and protein translocation is detected by confocal microscopy. Our approach has identified hsp90 as a partner protein that is associated, in part, with the restoration of p53 transcriptional transactivation function of PRIMA-1.

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Sensitivity to camptothecin of human breast carcinoma and normal endothelial cells

Abstract: The results suggest that cell cycle regulation plays an important role in determining the effect of CPT on malignant and normal cells. The possible mechanisms explaining the sensitivities of the two cellular compartments to the action of CPT are discussed.

Cited by 33 publications

References 20 publications

Optimized combinations of bortezomib, camptothecin, and doxorubicin show increased efficacy and reduced toxicity in treating oral cancer

Optimized combinations of bortezomib, camptothecin, and doxorubicin show increased efficacy and reduced toxicity in treating oral cancer

Potent Antiviral Activity of Topoisomerase I and II Inhibitors against Kaposi's Sarcoma-Associated Herpesvirus

Proteomics Characterization of the Molecular Mechanisms of Mutant P53 Reactivation with PRIMA-1 in Breast Cancer Cells

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