Document Detail

Adenosine triphosphate (ATP) enhances the antitumor effect of etoposide (VP16) in lung cancer cells.
MedLine Citation:
PMID:  15492806     Owner:  NLM     Status:  MEDLINE    
We have previously reported that adenosine triphosphate (ATP) enhances the cytotoxic effects of 4-hydroperoxycyclophosphamide (4HC) on leukemia cells without affecting the normal hematopoietic stem cells. Increased cell membrane permeability induced by ATP may cause high incorporation of 4HC into leukemia cells, ultimately leading to cell death. In the present study, we show that ATP has cytotoxicity against PC14, a lung adenocarcinoma cell line. When PC14 cells were cultured with 1, 3, and 5 mM ATP, colony number significantly decreased to 91.0, 48.8, and 2.3% respectively, compared to untreated controls. Additionally, ATP enhanced the antitumor effects of etoposide (VP16) in PC14 and another lung adenocarcinoma cell line, A549. With 5, 25, and 50 mM VP16, the percentage of colony numbers compared to control was 95.5, 75.8, and 61.3% in PC14 and 86.0, 65.0, and 57.1% in A549 cells, respectively. In the presence of 3 mM ATP, however, the colony number of PC14 was further limited to 49.6, 34.1, and 24.4% of the untreated level in 5, 25, and 50 mM VP16, respectively. When A549 cells were incubated with 1 mM ATP, the proportion of clonogeneic cells significantly fell to 62.5, 41.7, and 31.7% in 5, 25, and 50 mM VP16, respectively. With 3 and 5 mM of ATP, uptake of [3H]VP16 in PC14 cells increased respectively to 8.9- and 14.1-fold of the negative controls. These results suggest that ATP itself has antitumor effects on lung cancer cells and enhances the cytotoxicity of VP16 through the increased uptake of VP16 into the cells. The combined use of ATP and antitumor agents such as VP16 may have the potential to improve the therapeutic index in human lung carcinoma.
Yoshihiro Hatta; Miki Takahashi; Yuko Enomoto; Noriaki Takahashi; Umihiko Sawada; Takashi Horie
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncology reports     Volume:  12     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-19     Completed Date:  2004-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1139-42     Citation Subset:  IM    
Department of Hematology and Rheumatology, Nihon University School of Medicine, 30-1 Oyaguchi-kami-machi, Itabashi-ku, Tokyo 173-8610, Japan.
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MeSH Terms
Adenocarcinoma / metabolism,  pathology*
Adenosine Triphosphate / pharmacology*
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Drug Synergism
Drug Therapy, Combination
Etoposide / pharmacology*
Lung Neoplasms / metabolism,  pathology*
Tumor Cells, Cultured / drug effects
Tumor Stem Cell Assay
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 33419-42-0/Etoposide; 56-65-5/Adenosine Triphosphate

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