Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity.

Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity. Research Abstract Details 

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Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity. Abstract Text:

Etsuko Sakamoto,Sayaka Tsukioka,Shinji Oie,Takashi Kobunai,Hiroaki Tsujimoto,Kazuki Sakamoto,Yoshihiro Okayama,Yoshikazu Sugimoto,Toshinori Oka,Masakazu Fukushima,Tatsuzo Oka,Etsuko Sakamoto,Sayaka Tsukioka,Shinji Oie,Takashi Kobunai,Hiroaki Tsujimoto,Kazuki Sakamoto,Yoshihiro Okayama,Yoshikazu Sugimoto,Toshinori Oka,Masakazu Fukushima,Tatsuzo Oka,

Although 5-fluorouracil (5-FU) plus leucovorin (LV) is a standard chemotherapy regimen for colorectal cancer, the factors that determine the LV-mediated enhancement of the antitumor activity of 5-FU have remained unknown. We investigated the roles of folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH), which are the main enzymes involved in folate metabolism, in the effect of LV. LV enhanced the anticancer activity of 5-FU and the level of reduced folate in human colon cancer cells. Small-interfering RNA (siRNA) transfected into DLD-1 cells to downregulate FPGS reduced the basal level of reduced folate, the folate level after LV treatment, and the enhancement of 5-fluoro-2'-deoxyuridine (FdUrd)-induced cytotoxicity elicited by LV. By contrast, the downregulation of GGH by siRNA increased cellular sensitivity to FdUrd combined with LV. These results suggest that FPGS and GGH expression levels in tumors are determinants of the efficacy of LV in enhancing the antitumor activity of 5-FU.

Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity. Publishing Authors By Initials

E Sakamoto,S Tsukioka,S Oie,T Kobunai,H Tsujimoto,K Sakamoto,Y Okayama,Y Sugimoto,T Oka,M Fukushima,T Oka,E Sakamoto,S Tsukioka,S Oie,T Kobunai,H Tsujimoto,K Sakamoto,Y Okayama,Y Sugimoto,T Oka,M Fukushima,T Oka,

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Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochemical and biophysical research communication

VOLUME: 365

Page Numbers: 801-7

Journal Abbreviation: Biochem. Biophys. Res. Commun.

ISSN: 1090-2104

DAY: 21

MONTH: 11

YEAR: 2007

Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity. Information

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LANGUAGE: eng

NlmUniqueID: 372516

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Grant and Affiliation Information for Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity.

AFFILIATION: Department of Veterinary Medicine, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.

Country: United States

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MEDLINETA: Biochem Biophys Res Commun

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