Ovarian cancer therapeutic potential of glutamine depletion based on GS expression

Akiko Furusawa, Morikazu Miyamoto, Masashi Takano, Hitoshi Tsuda, Yong Sang Song, Daisuke Aoki, Naoyuki Miyasaka, Johji Inazawa, Jun Inoue

Research output: Contribution to journalArticle

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Abstract

Amino acids (AAs) are biologically important nutrient compounds necessary for the survival of any cell. Of the 20 AAs, cancer cells depend on the uptake of several extracellular AAs for survival. However, which extracellular AA is indispensable for the survival of cancer cells and the molecular mechanism involved have not been fully defined. In this study, we found that the reduction of cell survival caused by glutamine (Gln) depletion is inversely correlated with the expression level of glutamine synthetase (GS) in ovarian cancer (OVC) cells. GS expression was downregulated in 45 of 316 OVC cases (14.2%). The depletion of extracellular Gln by treatment with l-asparaginase, in addition to inhibiting Gln uptake via the knockdown of a Gln transporter, led to the inhibition of cell growth in OVC cells with low expression of GS (GSlow-OVC cells). Furthermore, the re-expression of GS in GSlow-OVC cells induced the inhibition of tumor growth in vitro and in vivo. Thus, these findings provide novel insight into the development of an OVC therapy based on the requirement of Gln.

Original languageEnglish
Pages (from-to)758-766
Number of pages9
JournalCarcinogenesis
Volume39
Issue number6
DOIs
Publication statusPublished - 2018 May 28

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Glutamate-Ammonia Ligase
Glutamine
Ovarian Neoplasms
Amino Acids
Cell Survival
Therapeutics
Asparaginase
Neoplasms
Growth
Down-Regulation
Food

ASJC Scopus subject areas

  • Cancer Research

Cite this

Furusawa, A., Miyamoto, M., Takano, M., Tsuda, H., Song, Y. S., Aoki, D., ... Inoue, J. (2018). Ovarian cancer therapeutic potential of glutamine depletion based on GS expression. Carcinogenesis, 39(6), 758-766. https://doi.org/10.1093/carcin/bgy033

Ovarian cancer therapeutic potential of glutamine depletion based on GS expression. / Furusawa, Akiko; Miyamoto, Morikazu; Takano, Masashi; Tsuda, Hitoshi; Song, Yong Sang; Aoki, Daisuke; Miyasaka, Naoyuki; Inazawa, Johji; Inoue, Jun.

In: Carcinogenesis, Vol. 39, No. 6, 28.05.2018, p. 758-766.

Research output: Contribution to journalArticle

Furusawa, A, Miyamoto, M, Takano, M, Tsuda, H, Song, YS, Aoki, D, Miyasaka, N, Inazawa, J & Inoue, J 2018, 'Ovarian cancer therapeutic potential of glutamine depletion based on GS expression', Carcinogenesis, vol. 39, no. 6, pp. 758-766. https://doi.org/10.1093/carcin/bgy033
Furusawa, Akiko ; Miyamoto, Morikazu ; Takano, Masashi ; Tsuda, Hitoshi ; Song, Yong Sang ; Aoki, Daisuke ; Miyasaka, Naoyuki ; Inazawa, Johji ; Inoue, Jun. / Ovarian cancer therapeutic potential of glutamine depletion based on GS expression. In: Carcinogenesis. 2018 ; Vol. 39, No. 6. pp. 758-766.
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