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

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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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Authors: Fuertes, M., Castilla, J., Alonso, C., & Pérez, J.
Affiliations: Universidad Autónoma de Madrid (ES)
Corresponding author: Castilla, J.
Pérez, J.
ORCID: Fuertes, M.
Alonso, C.
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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Cisplatin Biochemical Mechanism of Action: From Cytotoxicity to Induction of Cell Death Through Interconnections Between Apoptotic and Necrotic Pathways

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