Potential metabolomic biomarkers for evaluation of adriamycin efficacy using a urinary 1H-NMR spectroscopy.
A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c-nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg(-1) per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, ×0.3), hippurate (×0.3) and taurine (×0.6) decreased significantly (P < 0.05), whereas the levels of 3-indoxylsulfate (×12.6), trigonelline (×1.5), citrate (×2.5), trimethylamine (TMA, ×2.0) and 2-oxoglutarate (×2.3) increased significantly (P < 0.05) in the tumor model. After ADR treatment, TMAO, hippuarte and taurine were increased significantly on day 5 compared with those of the tumor model. The levels of 2-oxoglutarate, 3-indoxylsulfate, trigonelline, TMA and citrate, which increased in the tumor model, significantly decreased to those of normal control by ADR treatment. Furthermore, the ratio between TMA and TMAO was dramatically altered in both tumor and ADR-treated groups. Overall, metabolites such as TMAO, TMA, 3-indoxylsulfate, hippurate, trigonelline, citrate and 2-oxoglutarate related to the tricarboxylic acid (TCA) cycle might be considered as therapeutic targets to potentiate the efficacy of ADR. Thus, these results suggest that the metabolomics analysis of tumor response to ADR treatment may be applicable for demonstrating the efficacy of anticancer agent, ADR and treatment adaptation.
College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam, 330-714, Korea.
Kyu-Bong
KB
Kim
Ji-Young
JY
Yang
Seung Jun
SJ
Kwack
Hyung Sik
HS
Kim
Do Hyun
DH
Ryu
Yeon-Joo
YJ
Kim
Jung Yun
JY
Bae
Duck Soo
DS
Lim
Seul Min
SM
Choi
Mi Jung
MJ
Kwon
Du Yeon
DY
Bang
Seong Kwang
SK
Lim
Young Woo
YW
Kim
Geum-Sook
GS
Hwang
Byung-Mu
BM
Lee
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000652:urine*; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D004317:Doxorubicin