Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Oct 5:740:364-78.
doi: 10.1016/j.ejphar.2014.07.025. Epub 2014 Jul 21.

Cisplatin in cancer therapy: molecular mechanisms of action

Shaloam Dasari  1 , Paul Bernard Tchounwou  2
Affiliations
Review

Cisplatin in cancer therapy: molecular mechanisms of action

Shaloam Dasari et al. Eur J Pharmacol. .

Abstract

Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is paid to its molecular mechanisms of action, and its undesirable side effects.

Keywords: Cancer treatment; Cisplatin; Mechanisms of action; Platinum-based drugs.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Chemical structures of selected platinum drugs: A-cisplatin; B-carboplatin; C-oxaliplatin; D-ormaplatin; E-enloplatin (Weiss and Christian, 1993).
Fig. 2
Fig. 2
Computational molecular structures of cisplatin, carboplatin and oxaliplation. These platinum compounds are composed of doubly charged platinum ion surrounded by four ligands; with the amine ligands on the left forming stronger interactions with the platinum ion, and the chloride ligands or carboxylate compounds on the right forming leaving groups allowing the platinum ion to form bonds with DNA bases (Goodsell, 2006).
Fig. 3
Fig. 3
Overview of molecular mechanisms of cisplatin in cancer treatment.
See this image and copyright information in PMC

References

    1. Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM. SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol.Cancer Ther. 2003;2:471–478. - PubMed
    1. Agarwal R, Kaye SB. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat.Rev.Cancer. 2003;3:502–516. - PubMed
    1. Aggarwal SK. A histochemical approach to the mechanism of action of cisplatin and its analogues. J.Histochem.Cytochem. 1993;41:1053–1073. - PubMed
    1. Aggarwal SK. Calcium modulation of toxicities due to Cisplatin. Met.Based.Drugs. 1998;5:77–81. - PMC - PubMed
    1. Aggarwal SK, Broomhead JA, Fairlie DP, Whitehouse MW. Platinum drugs: combined anti-lymphoproliferative and nephrotoxicity assay in rats. Cancer Chemother.Pharmacol. 1980;4:249–258. - PubMed

Publication types

MeSH terms