Anti-tumor effect of N-beta-alanyl-5-S-glutathionyldihydroxyphenylalanine (5-S-GAD), a novel anti-bacterial substance from an insect.
OBJECTIVE
We examined the anti-tumor effect of 5-S-GAD, a novel potent inhibitor of protein tyrosine kinases, isolated from the flesh fly in order to investigate the potential use of this compound as an anti-tumor agent.


METHODS
In vitro growth inhibition was evaluated using the alamarBlue assay kit. In vivo anti-tumor activity was evaluated by i.p. treatment of 5-S-GAD against xenografted melanoma (LOX-IMV1) and breast carcinoma (MDA-MB-435S) in nude mice.


RESULTS
Of 38 human cancer cell lines examined, this compound showed significant cytotoxicity toward two estrogen-negative breast carcinomas (MDA-MB-231 and MDA-MB-435S) and one malignant melanoma (LOX-IMV1) in vitro, indicating that it exhibits selective cytotoxicity to certain tumor cell lines. In accordance with its in vitro anti-tumor effect, 5-S-GAD was shown to significantly repress the growth of sensitive tumor cells in nude mice.


CONCLUSIONS
These results indicate that 5-S-GAD is potentially useful to treat certain human cancer.
Akiyama
N
N
Natori Special Laboratory, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Hijikata
M
M
Kobayashi
A
A
Yamori
T
T
Tsuruo
T
T
Natori
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016227:Benzoquinones; D001943:Breast Neoplasms / Q000473:pathology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004175:Diptera / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D047029:Lactams, Macrocyclic; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008545:Melanoma / Q000473:pathology*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009368:Neoplasm Transplantation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation
D000970:Antineoplastic Agents; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; C100496:N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine; D009363:Neoplasm Proteins; D011809:Quinones; D017828:Rifabutin; D004295:Dihydroxyphenylalanine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D005978:Glutathione