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Research ArticleExperimental Studies

In Vitro and In Vivo Efficacy of a Novel Quinuclidinone Derivative Against Breast Cancer

AHMED MALKI and EL SAYED EL ASHRY
Anticancer Research March 2014, 34 (3) 1367-1376;
AHMED MALKI
1Department of Health Sciences, Biomedical Sciences Program, Faculty of Science, College of Arts and Sciences, Qatar University, Doha, Qatar
2Biochemistry Department, Alexandria University, Alexandria, Egypt
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  • For correspondence: ahmed.malki@qu.edu.qa
EL SAYED EL ASHRY
3Chemistry Department Faculty of Science, Alexandria University, Alexandria, Egypt
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Abstract

Previously, our laboratory reported on novel quinuclidinone derivatives that cause cytotoxicity in human non-small lung carcinoma epithelial cells null for p53 (H1299). The current study aims to investigate the effect of novel designed quinuclidinone derivatives on cytotoxicity towards human MCF-7 breast cancer cells, normal breast epithelial cells (MCF-12a) and an animal model of breast cancer. Quinuclidinone 2 induced growth inhibition mainly through apoptosis in breast cancer cells (MCF-7), with less cytotoxic effects towards normal breast epithelial cells (MCF-12a) compared to the other derivatives. Our novel quinuclidinone-2 increased expression of p53 and cyclin-D and reduced expression levels of (Mdm2), (Bcl-2) and (Akt). It also reduced expression of (Bax) as down stream target of p53 at both RNA and protein levels. Additionally, quinuclidinone 2 induced G1 phase arrest presumably sensitizing breast cancer cells to apoptosis by increasing expression of p21. In vivo studies were performed to assess the anticancer effect of quinuclidinone 2 on N-Nitroso-N-methylurea-induced breast cancer in female rats by evaluating physiological processes and the expression levels of β-catenin and E-cadherin. The approximate lethal dose of quinuclidinone 2 was determined to be 90 mg/kg and it led to significant reduction in tumor size compared to the untreated group. In vivo studies revealed that quninuclidinone derivative 6 does not induce any apparent toxicity towards the treated hosts and under the present experimental set up seems to be a promising candidate for further evaluation in cancer therapy

  • Anticancer drugs
  • p53
  • Bax
  • p21
  • E-Cadherin
  • cell cycle
  • breast cancer
  • Received August 13, 2013.
  • Revision received September 27, 2013.
  • Accepted October 1, 2013.
  • Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 34 (3)
Anticancer Research
Vol. 34, Issue 3
March 2014
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In Vitro and In Vivo Efficacy of a Novel Quinuclidinone Derivative Against Breast Cancer
AHMED MALKI, EL SAYED EL ASHRY
Anticancer Research Mar 2014, 34 (3) 1367-1376;

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In Vitro and In Vivo Efficacy of a Novel Quinuclidinone Derivative Against Breast Cancer
AHMED MALKI, EL SAYED EL ASHRY
Anticancer Research Mar 2014, 34 (3) 1367-1376;
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Keywords

  • Anticancer drugs
  • p53
  • bax
  • p21
  • e-cadherin
  • cell cycle
  • breast cancer
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