cisplatin


OTHER NAMES:
Platinol


ABBREVIATIONS:
CDDP


DESCRIPTION: Cisplatin, cisplatinum, or cis-diamminedichloroplatinum(II) (CDDP) (trade names Platinol and Platinol-AQ) is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas, and germ cell tumors. It was the first member of a class of platinum-containing anti-cancer drugs, which now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and causing crosslinking of DNA, which ultimately triggers apoptosis (programmed cell death).
Of the bases on DNA, guanine is preferred. Subsequent to formation of [PtCl(guanine-DNA)(NH3)2]+, crosslinking can occur via displacement of the other chloride ligand, typically by another guanine. Cisplatin crosslinks DNA in several different ways, interfering with cell division by mitosis. The damaged DNA elicits DNA repair mechanisms, which in turn activate apoptosis when repair proves impossible.
Most notable among the changes in DNA are the 1,2-intrastrand cross-links with purine bases. These include 1,2-intrastrand d(GpG) adducts which form nearly 90% of the adducts and the less common 1,2-intrastrand d(ApG) adducts. 1,3-intrastrand d(GpXpG) adducts occur but are readily excised by the nucleotide excision repair (NER). Other adducts include inter-strand crosslinks and nonfunctional adducts that have been postulated to contribute to cisplatin's activity. Interaction with cellular proteins, particularly HMG domain proteins, has also been advanced as a mechanism of interfering with mitosis, although this is probably not its primary method of action.

Platinol® - the anticancer drug that specifically targest DNA; chemotherapeutic; forms crosslinks. Cisplatin is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, small cell lung cancer, ovarian cancer, lymphomas, and germ cell tumors. It was the first member of a class of anti-cancer drugs which now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and causing crosslinking of DNA which ultimately triggers apoptosis.

DNA DAMAGES:
intErstrand crosslinks (ICLs)
intrAstrand crosslink


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NAME STRUCTURE PROTEINS DNA DAMAGE EFFECT(S) PATHWAY(S) RELATED
intErstrand crosslinks (ICLs) UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
MUS81
EME1
ERCC1
SLX4
SLX1A
SLX1B
TOP3A
cell cycle arrest
DNA backbone distortion
mutagenesis
stalled replication fork
Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
homologous recombination (HR)
DNA replication
intrAstrand crosslink UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
cell cycle arrest
DNA backbone distortion
stalled replication fork
Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response

References:

  • Cisplatin cytotoxicity: DNA and plasma membrane targets.
    Rebillard A., Lagadic-Gossmann D., Dimanche-Boitrel MT.
    Curr. Med. Chem., 2008 , 15:2656-63 [PUBMED]

Last modification date: Oct. 12, 2011