Cisplatin biochemical mechanism of action. 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 andor DNA replication mechanisms.

Schematic Representation Of Mechanism Of Action Of Cisplatin Download Scientific Diagram

It was shown that cytotoxic activity of cisplatin in the samples studied was preserved for 1 month.

Cisplatin mechanism of action. From cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Studies have revealed that cisplatin does not affect RNA synthesis but that it does affect DNA synthesis. Cisplatin causes cells to arrest at either the G1 S or G2phase of the cell cycle in an attempt to repair the damage.

If cisplatin-DNA adducts are not efficiently processed by cell machinery cytotoxic processes eventually end up in cell death. The second group of mechanisms includes enhanced repair of DNA adducts of cisplatin and increased tolerance of the resulting DNA damage. While triggering apoptosis through interfering with DNA replication remains the primary mechanism of cisplatin this has not been found to contribute to neurological side effects.

Mechanism of Action Cisplatin is believed to kill cancer cells by binding to DNA and interfering with its repair mechanism eventually leading to cell death. Using a CCK-8 cell viability assay we found all three BC cell lines that were transfected with HOXA-AS3 siRNA had increased cisplatin sensitivity compared with the negative controls Figures 2BE while the HOXA-AS3 plasmid had reduced cisplatin sensitivity Supplemental. Cisplatin Accession Number DB00515 Description.

Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA. The first step in the process after the cisplatin molecule penetrates the cell membrane intact is for a molecule of water to replace one of the chloride ions. Recent studies have shown that cisplatin noncompetitively inhibits an archetypal membrane-bound mechanosensitive sodium-hydrogen ion transporter known as NHE-1.

From Cytotoxicity to Induction of Cell Death Through Interconnections Between Apoptotic and Necrotic Pathways VOLUME. Cisplatin is a platinum-based chemotherapy medicine used to treat a variety of cancers including bladder cancer cervical cancer head and neck cancer lung cancer testicular cancer and cancer. Perez AffiliationDepartamento de Quimica Inorganica Facultad de Ciencias Universidad Autonoma de Madrid Cantoblanco 28049-Madrid Spain.

The mechanism of its antitumor action is related to bifunctional alkylating of DNA chains which suppresses biosynthesis of nucleic acids and induces cell apoptosis. First a single damaged RNA molecule can be replaced by newly synthesized material. The mechanism of action of cisplatin has been associated with ability to crosslink with the urine bases on the DNA to form DNA adducts preventing repair of the DNA leading to DNA damage and subsequently induces apoptosis within cancer cells.

Cisplatin cisplatinum or cis-diamminedichloroplatinumII CDDP is a platinum-based chemotherapy drug used to treat various types of cancers including sarcomas some carcinomas eg. Small cell lung cancer and ovarian cancer lymphomas and germ cell tumors. Cisplatin Biochemical Mechanism of Action.

Cisplatin is in a class of drugs known as platinum-containing compounds used to treat various types of cancers including metastatic testicular and ovarian tu. Cisplatin exerts anticancer effects via multiple mechanisms yet its most prominent and best understood mode of action involves the generation of DNA lesions followed by the activation of the DNA. However the mechanism by which these adducts kill cells is less well understood.

Although cisplatin can coordinate to RNA this interaction is not believed to play an important role in cisplatins mechanism of action in the body for two reasons. The proposed mechanisms of cisplatin resistance include changes in cellular uptake and efflux of cisplatin increased biotransformation and detoxification in the liver and increase in DNA repair and anti-apoptotic mechanisms Gottesman et al 2002. Cisplatin CP is a platinum-based antitumor preparation.

Cisplatin is well known as a DNAdamaging agent and the specific adducts produced in DNA have been well characterized. Interfering with DNA repair mechanisms causing DNA damage and subsequently inducing apoptosis in cancer cells. It is effective against various types of cancers including carcinomas germ cell tumors lymphomas and sarcomas.

In human cells cisplatin intrastrand adducts are removed from DNA mainly by the nucleotide excision repair NER system11 It has been found using cellfree extracts or a reconstituted NER system that intrastrand cross-links of cisplatin are efficiently repaired. Next we examined the effect of HOXA-AS3 on cisplatin sensitivity and its potential mechanism of action in BC cells.