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Title 

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

Authors 

Doo Jin KimEn Jin KimTae Young LeeJi Na WonM H SungHaryoung Poo

Publisher 

The Korean Society for Applied Microbiology

Issue Date 

2013

Citation 

Journal of Microbiology and Biotechnology, vol. 23, no. 9, pp. 1339-1346

Keywords 

Antitumor effectCyclophosphamideMetastasisNatural killer cellsPoly-gamma-glutamate

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.

ISSN 

1017-7825

Link 

http://dx.doi.org/10.4014/jmb.1306.06071

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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