Description
(+)-
Aphidicolin is a natural tetracyclic diterpene first isolated from the fungus
C. aphidicola and shown to have antiviral activity against herpes simplex. In eukaryotic cells, it is a cell-
permeable, reversible inhibitor of DNA replication, specifically blocking the activity of DNA polymerases α, δ, and ε when used at low micromolar levels. Aphidicolin can be used, at 3 μM, to arrest cells in G
1/S phase or to increase gene amplification frequency.
Chemical Properties
White crystal
Uses
A DNA polymerase inhibitor. Blocks the cell cycle at the early S-phase
Uses
Aphidicolin is a tetracyclic diterpene antibiotic isolated from fungi, notably Cephalosporium, Nigrospora, Harziella and Phoma. Aphidicolin has antibiotic, antiviral and antimitotic properties, blocking the cell cycle at early S-phase. This property has been used to synchronise cell division and is useful as a tool in cell differentiation research. Aphidicolin is a reversible inhibitor of DNA replication by inhibiting selected DNA polymerases. Aphidicolin induces apoptosis, prolongs the half-life of DNA methyltransferase, is active against Leishmania parasites and acts synergistically with the antitumour agents, vincristine and doxorubicin.
Uses
(+)-Aphidicolin is a naturally occurring tetracyclic diterpene with potential antiviral and antimitotical properties.
Definition
ChEBI: A tetracyclic diterpenoid that has an tetradecahydro-8,11a-methanocyclohepta[a]naphthalene skeleton with two hydroxymethyl substituents at positions 4 and 9, two methyl substituents at positions 4 and 11b and two hydroxy substituents at positi
ns 3 and 9. An antibiotic with antiviral and antimitotical properties. Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication.
General Description
A cell-permeable tetracyclic diterpene antibiotic. Cell synchronization agent. Blocks the cell cycle at the early S-phase. Specific inhibitor of DNA polymerase α and δ in eukaryotic cells and in some viruses of animal origin. Potentiates apoptosis induced by arabinosyl nucleosides in leukemia cell lines. Also induces apoptosis in HeLaS3 cells, but inhibits vincristine-induced apoptosis in the p53-negative human prostate cancer cell line PC-3.
Biochem/physiol Actions
Cell permeable: yes
References
1) Syvaoja et al. (1990), DNA polymerases alpha, delta, and epsilon: three distinct enzymes from HeLa cells; Proc. Natl. Acad. Sci. USA, 87 6664
2) Urbani et al. (1995), Dissociation of nuclear and cytoplasmic cell cycle progression by drugs employed in cell synchronization; Exp. Cell Res., 219 159
3) Kuwakado et al. (1993), Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human myeloid leukemia cell lines; Biochem. Pharmacol., 46 1909
4) Yin and Schimke (1996), Inhibition of apoptosis by overexpressing Bcl-2 enhances gene amplification by a mechanism independent of aphidicolin pretreatment; Proc. Natl. Acad. Sci. USA, 93 3394
