Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023418 (
leukemia
)
93,477
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have evaluated the chemotherapeutic potential of
2,4-dihydroxyphenylalanine
, a targeted prodrug that can be hydroxylated by tyrosinase (monophenol monooxygenase, EC 1.14.18.1) within melanoma cells to form the cellular toxin 2,4,5-trihydroxyphenylalanine (6-hydroxydopa). 2,4-Dihydroxyphenylalanine proved to be cytotoxic to both B-16 and Cloudman melanoma cells in vitro. The immediate effects of
2,4-dihydroxyphenylalanine
included inhibition of DNA, RNA, and protein syntheses. In contrast, no decrease in macromolecular synthesis or viability was seen against cultures of MJY-alpha mammary tumor or L-1210
leukemia
, two cell types that do not contain tyrosinase. Within the melanoma cultures, greater cytotoxicity was seen against melanotic (tyrosinase-containing) cells than against amelanotic (tyrosinase-lacking) cells. The cytotoxicity of
2,4-dihydroxyphenylalanine
was blocked by 1-phenylthiourea, an inhibitor of tyrosinase. These results show that
2,4-dihydroxyphenylalanine
is toxic to melanoma cells and that activation of
2,4-dihydroxyphenylalanine
requires the presence of tyrosinase.
...
PMID:In vitro studies of 2,4-dihydroxyphenylalanine, a prodrug targeted against malignant melanoma cells. 392 68
