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Cited by 432Metal complexes synthesis and propertiesCell death mechanisms and regulationCancer therapeutics and mechanisms

The DOI matches its Crossref record.

Cisplatin Biochemical Mechanism of Action: From Cytotoxicity to Induction of Cell Death Through Interconnections Between Apoptotic and Necrotic Pathways

Fuertes, M., Castilla, J., Alonso, C., Pérez, J.·2003·Current Medicinal Chemistry
DOI 10.2174/0929867033368484
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Abstract

Although cisplatin, cis-diamminedichloroplatinum(II), has been successfully used in the chemotherapy of cancer for more than 25 years, its biochemical mechanism of action is still unclear. The current accepted paradigm about cisplatin mechanism of action is that the drug induces its cytotoxic properties through binding to nuclear DNA and subsequent interference with normal transcription, and/or DNA replication mechanisms. If cisplatin-DNA adducts are not efficiently processed by cell machinery, cytotoxic processes eventually end up in cell death. However, before cisplatin enters the cell it may bind to phospholipids and phosphatidylserine in the cell membrane. In addition, in the cytoplasm many potential platinum-binding sites are also available, including RNA and sulfur-containing biomolecules. Moreover, there is much evidence suggesting that the cytotoxic effects induced by binding of cisplatin to non-DNA targets (especially proteins) may contribute to its biochemical mechanism of action. On the other hand, it has been found that several factors such as the dose of drug as well as the metabolic condition of the cell subjected to cisplatin aggression, may determine that cancer cells die through apoptosis or necrosis. In fact, it has recently been reported that both mechanisms of cell demise work in concert so that within a population of tumour cells there is a continuum of possible modes of cell death.

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Metadata

Authors
Fuertes, M., Castilla, J., Alonso, C., & Pérez, J.
Affiliations
Universidad Autónoma de Madrid (ES)
Corresponding author
  • Castilla, J.
  • Pérez, J.
ORCID
Venue
Current Medicinal Chemistry
Publisher
Bentham Science Publishers Ltd.
Published
2003-02-01
Volume
10
Issue
3
Pages
257-266
ISSN
0929-8673 (ISSN-L)
DOI
10.2174/0929867033368484
OpenAlex
W2146133266
Cited by
432
References
0
Citations by year
2026: 3 · 2025: 14 · 2024: 31 · 2023: 38 · 2022: 21 · 2021: 14 · 2020: 17 · 2019: 13 · 2018: 15 · 2017: 21 · 2016: 22 · 2015: 15 · 2014: 30 · 2013: 28 · 2012: 27
FWCI
5.98
Type
journal article
Language
en
Open access
closed
Locations
  • Current Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
Fundación Ramón Areces
Topics
  • Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
Keywords
cisplatin, mechanism of action, DNA adducts, phospholipid binding, phosphatidylserine, RNA binding, cytotoxicity, apoptosis, necrosis, cell death pathways, platinum-based chemotherapy
MeSH terms
Animals, Antineoplastic Agents, Binding Sites, Cisplatin, DNA Damage, DNA Repair, Humans, Necrosis, Neoplasms, Cell Death, Apoptosis

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