alexa Enhancing Doxorubicin-Induced MCA-Fibrosarcoma Cytotoxicity by an Eriobotrya japonica Hydrophilic Butanol-Treated Extract through Natural Killer Cells Activation
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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Research Article

Enhancing Doxorubicin-Induced MCA-Fibrosarcoma Cytotoxicity by an Eriobotrya japonica Hydrophilic Butanol-Treated Extract through Natural Killer Cells Activation

Khalid Z Matalka1*, Marwa T Alsaadi1, Nidal Qinna1, Eyad Mallah2, Riad Awad2, Wael Abu Dayyih2, Tawfiq Alhussainy1 and Fadi Qadan2
1Department of Pharmacology and Biomedical Sciences Petra University, Amman, Jordan
2Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan
Corresponding Author : Khalid Z Matalka
Department of Pharmacology and Biomedical Sciences
Petra University, Amman, Jordan
Tel: (00962-6) 5715546-5715549
Fax: 5715561-5715570
E-mail: [email protected]
Received November 05, 2012; Accepted December 12, 2012; Published December 14, 2012
Citation: Matalka KZ, Alsaadi MT, Qinna N, Mallah E, Awad R, et al. (2012) Enhancing Doxorubicin-Induced MCA-Fibrosarcoma Cytotoxicity by an Eriobotrya japonica Hydrophilic Butanol-Treated Extract through Natural Killer Cells Activation. J Cancer Sci Ther S18:003. doi: 10.4172/1948-5956.S18-003
Copyright: © 2012 Matalka KZ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

The combination of cytotoxic drugs with immunotherapy should be more effective than monotherapy alone since both therapeutic modalities may target different mechanisms. In addition, combination therapy may reduce adverse events associated with cytotoxic drugs. Eriobotrya japonica hydrophilic butanol-treated extract (EJWR) was found to modulate cytokines by enhancing IL-12, IFN-γ and TNF-α in vitro and in vivo and within tumor microenvironment. This was associated with enhancing survival time of mice bearing intra-peritoneal MCA fibrosarcoma (MCA FS). In the present work, we evaluated the combination of EJWR with doxorubicin (Dox) on MCA FS cytotoxicity using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay in the absence and presence of spleen cells or Natural Killer (NK) lymphocytes from tumor bearing mice. The results showed that Dox exhibited mild cytotoxicity to healthy spleen cells and EJWR reversed such cytotoxicity. In addition, increasing concentrations of Dox induced 40% (p<0.01) MCA FS cytotoxicity. This percent increased significantly to 60% at Dox 5 μM when co-cultured with NK cells from tumor bearing mice and increased further to 80% (p<0.01) when Dox was combined with EJWR. The latter increase in cytotoxicity was significantly (p<0.01) higher than each agent alone. This enhancement was associated with significant production of TNF-α and retaining IFN-γ levels from NK cells lysates. This concluded that the immunomodulator, EJWR, mediates NK activation and enhances Dox- induced MCA FS cytotoxicity.

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