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Sensitization of cancer cells to DNA damaging agents by imidazolines.

Apoptosis, or programmed cell death, is a cellular mechanism used to regulate cell number and eliminate damaged or mutated cells. Concomitant with the initiation of the apoptotic cell signal, chemotherapeutic agents also induce anti-apoptotic factors, such as NF- Kappa B, which compromise the overal... Full description

Journal Title: Journal of the American Chemical Society July 19, 2006, Vol.128(28), pp.9137-9143
Main Author: Sharma, Vasudha
Other Authors: Peddibhotla, Satyamaheshwar , Tepe, Jetze J
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0002-7863
Link: http://search.proquest.com/docview/68635199/?pq-origsite=primo
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recordid: proquest68635199
title: Sensitization of cancer cells to DNA damaging agents by imidazolines.
format: Article
creator:
  • Sharma, Vasudha
  • Peddibhotla, Satyamaheshwar
  • Tepe, Jetze J
subjects:
  • Antineoplastic Agents–Pharmacology
  • Apoptosis–Drug Effects
  • Camptothecin–Pharmacology
  • Cell Line, Tumor–Pharmacology
  • Cisplatin–Drug Effects
  • DNA Damage–Drug Effects
  • Gene Expression Regulation, Neoplastic–Pharmacology
  • Humans–Pathology
  • Imidazolines–Pathology
  • Models, Molecular–Pathology
  • Molecular Structure–Pathology
  • Neoplasms–Pathology
  • Structure-Activity Relationship–Pathology
  • Antineoplastic Agents
  • Imidazolines
  • Cisplatin
  • Camptothecin
ispartof: Journal of the American Chemical Society, July 19, 2006, Vol.128(28), pp.9137-9143
description: Apoptosis, or programmed cell death, is a cellular mechanism used to regulate cell number and eliminate damaged or mutated cells. Concomitant with the initiation of the apoptotic cell signal, chemotherapeutic agents also induce anti-apoptotic factors, such as NF- Kappa B, which compromise the overall efficacy of chemotherapeutic anticancer treatment. Here we describe an adjuvant therapy in which a small molecule is used to sensitize cancer cells toward apoptosis induced by chemotherapeutics. Our results indicate that the imidazoline 1d modulates the pro-survival NF- Kappa B pathway and selectively sensitizes cancer cells toward DNA damaging agents, thus enhancing the overall efficacy of the treatment. Pretreatment of cancer cells with the noncytotoxic imidazoline 1d (10 nM) resulted in a significant increase in apoptosis and anticancer efficacy of the clinically significant DNA damaging agents camptothecin and cisplatin. Noncancerous cells remained unaffected during this regimen.
language: eng
source:
identifier: ISSN: 0002-7863
fulltext: no_fulltext
issn:
  • 00027863
  • 0002-7863
url: Link


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titleSensitization of cancer cells to DNA damaging agents by imidazolines.
creatorSharma, Vasudha ; Peddibhotla, Satyamaheshwar ; Tepe, Jetze J
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ispartofJournal of the American Chemical Society, July 19, 2006, Vol.128(28), pp.9137-9143
identifierISSN: 0002-7863
subjectAntineoplastic Agents–Pharmacology ; Apoptosis–Drug Effects ; Camptothecin–Pharmacology ; Cell Line, Tumor–Pharmacology ; Cisplatin–Drug Effects ; DNA Damage–Drug Effects ; Gene Expression Regulation, Neoplastic–Pharmacology ; Humans–Pathology ; Imidazolines–Pathology ; Models, Molecular–Pathology ; Molecular Structure–Pathology ; Neoplasms–Pathology ; Structure-Activity Relationship–Pathology ; Antineoplastic Agents ; Imidazolines ; Cisplatin ; Camptothecin
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descriptionApoptosis, or programmed cell death, is a cellular mechanism used to regulate cell number and eliminate damaged or mutated cells. Concomitant with the initiation of the apoptotic cell signal, chemotherapeutic agents also induce anti-apoptotic factors, such as NF- Kappa B, which compromise the overall efficacy of chemotherapeutic anticancer treatment. Here we describe an adjuvant therapy in which a small molecule is used to sensitize cancer cells toward apoptosis induced by chemotherapeutics. Our results indicate that the imidazoline 1d modulates the pro-survival NF- Kappa B pathway and selectively sensitizes cancer cells toward DNA damaging agents, thus enhancing the overall efficacy of the treatment. Pretreatment of cancer cells with the noncytotoxic imidazoline 1d (10 nM) resulted in a significant increase in apoptosis and anticancer efficacy of the clinically significant DNA damaging agents camptothecin and cisplatin. Noncancerous cells remained unaffected during this regimen.
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