What is cisplatin DNA?
Cisplatin, a DNA-damaging agent, is one of the most widely used anticancer drugs. As with all members of this class of chemotherapeutic compounds, the clinical success of cisplatin is compromised if tumor cells become resistant by various mechanisms, including enhanced DNA repair.
What kind of DNA damage does cisplatin cause?
It kills cancer cells by damaging their DNA, mainly by forming Pt-d(GpG) and, to a lesser extent, Pt-d(ApG), Pt-d(GpXpG) intrastrand diadduct, and at lower frequency, Pt-G-G interstrand cross-links (2–4).
What happens when the DNA repair enzymes locate the DNA cisplatin adducts?
Cisplatin-induced intrastrand adducts are bulky lesions that interfere with DNA replication machinery by arresting replicative DNA polymerases. The prolonged stalling of replication forks can result in the formation of DNA DSBs, and such deleterious damage can lead to gross DNA rearrangements or cell death 60.
How does cisplatin inhibit DNA replication?
Cisplatin binds covalently to DNA, which trigger inhibition of DNA replication, causing cell cycle arrest in the S/G2 phase32.
How is cisplatin used to treat cancers?
Cisplatin binds to the N7 reactive center on purine residues and as such can cause deoxyribonucleic acid (DNA) damage in cancer cells, blocking cell division and resulting in apoptotic cell death.
How good is cisplatin?
In particular, cisplatin’s success as a chemotherapy drug against testicular cancer is phenomenal. When used in combination with other chemotherapy drugs, its cure rate is more than 90 percent.
How do you know if cisplatin is working?
Monitoring and Testing While Taking Cisplatin: Periodic blood work will be obtained to monitor your complete blood count (CBC) your electrolytes (such as calcium, magnesium, potassium, and sodium levels) as well as the function of other organs (such as your kidneys and liver) will also be ordered by your doctor.
How effective is cisplatin?
Does cisplatin cause double strand breaks?
Cisplatin treatment results in persistent DNA DSBs and has no effect on the repair of IR-induced DNA single-strand breaks (20).
What is the purpose of cisplatin?
Cisplatin, a chemotherapy drug, is best known for curing testicular cancer. It is also used in the treatment of a wide range of other cancers, including lung, bladder, cervical, and ovarian cancers. Cisplatin and other similar platinum-based drugs were developed with National Cancer Institute (NCI) support.
Why is cisplatin toxic?
Cisplatin causes damage to nuclear and mitochondrial DNA and production of reactive oxygen species (ROS) which lead to activation of both mitochondrial and non-mitochondrial pathways of apoptosis and necrosis. Mitochondrial energetics are also disrupted by cisplatin and may contribute to nephrotoxicity.