Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways.

doi:10.2174/0929867033368484

Paper

Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways.

Published Jan 31, 2003 · M. Fuertes, J. Castilla, C. Alonso

Current medicinal chemistry

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417

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12

Influential Citations

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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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Study Snapshot

Cisplatin's cytotoxic properties may involve binding to non-DNA targets, affecting cell death through apoptosis or necrosis, and its effectiveness depends on factors such as drug dose and cell metabolic condition.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways.

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References

Citations

Modulation of Brain Kynurenic Acid by N-Acetylcysteine Prevents Cognitive Impairment and Muscular Weakness Induced by Cisplatin in Female Rats

NAC can prevent cognitive impairment and muscle weakness caused by cisplatin treatment in female rats by improving redox imbalance and modulating brain kynurenic acid levels.

Cisplatin-Functionalized Dual-Functional Bone Substitute Granules for Bone Defect Treatment after Bone Tumor Resection.

Cisplatin-functionalized bone substitute granules show promise for local treatment of bone defects after bone tumor resection, offering a safe and potentially more effective alternative to systemic cisplatin administration.

DNA or not DNA -that is the question determining the design of platinum anticancer drugs.

Platinum anticancer drugs can exhibit antitumor activity through diverse mechanisms, breaking the classical DNA-only paradigm and offering opportunities for innovative drug design.

Melatonin Mitigates Cisplatin-Induced Submandibular Gland Damage by Inhibiting Oxidative Stress, Inflammation, Apoptosis, and Fibrosis

Melatonin reduces cisplatin-induced submandibular damage by inhibiting oxidative stress, inflammation, and fibrosis, potentially benefiting clinical applications.

CDKN1A Promotes Cis-induced AKI by Inducing Cytoplasmic ROS Production and Ferroptosis.

CDKN1A is a potential biomarker for cisplatin-induced acute kidney injury, offering new therapeutic insights and aiding in early diagnosis and intervention.

Nanoparticles constructed from natural polyphenols are used in acute kidney injury.

Polyphenol nanoparticles show promising effects in reducing kidney injury, improving renal function, and promoting renal tissue repair in acute kidney injury treatment.