Combination of poly-gamma-glutamate and cyclophosphamide enhanced antitumor efficacy against tumor growth and metastasis in a melanoma model

Cited 6 time in scopus
Metadata Downloads
Title
Combination of poly-gamma-glutamate and cyclophosphamide enhanced antitumor efficacy against tumor growth and metastasis in a melanoma model
Author(s)
Doo Jin Kim; En Jin Kim; Tae Young Lee; Ji Na Won; M H Sung; Haryoung Poo
Bibliographic Citation
Journal of Microbiology and Biotechnology, vol. 23, no. 9, pp. 1339-1346
Publication Year
2013
Abstract
Conventional chemotherapeutic regimens often accompany severe side effects and fail to induce complete regression of chemoresistant or relapsing metastatic cancers. The need for establishing more efficacious anticancer strategies led to the development of a combined modality treatment of chemotherapy in conjunction with immunotherapy or radiotherapy. It has been reported that poly-gamma-glutamate (γ-PGA), a natural polymer composed of glutamic acids, increases antitumor activity by activating antigen-presenting cells and natural killer (NK) cells. Here, we investigated the antitumor effect of γ-PGA in combination with cyclophosphamide in a murine melanoma model. Whereas cyclophosphamide alone directly triggered apoptosis of tumor cells in vitro, γ-PGA did not show cytotoxicity in tumor cells. Instead, it activated macrophages, as reflected by the upregulation of surface activation markers and the secretion of proinflammatory factors, such as nitric oxide and tumor necrosis factor α. When the antitumor effects were examined in a mouse model, combined treatment with cyclophosphamide and γ-PGA markedly suppressed tumor growth and metastasis. Notably, γ-PGA treatment dramatically increased the NK cell population in lung tissues, coinciding with decreased metastasis and increased survival. These data collectively suggest that γ-PGA can act as an immunotherapeutic agent that exhibits a synergistic antitumor effect in combination with conventional chemotherapy.
Keyword
Antitumor effectCyclophosphamideMetastasisNatural killer cellsPoly-gamma-glutamate
ISSN
1017-7825
Publisher
South Korea
DOI
http://dx.doi.org/10.4014/jmb.1306.06071
Type
Article
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.