How does cisplatin work mechanism?

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.

How does cisplatin target cancer cells?

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. The 1,2-intrastrand cross-links of purine bases with cisplatin are the most notable among the changes in DNA.

How does cisplatin block cell proliferation?

Specifically, cisplatin binds DNA and causes DNA inter- or intra-strand crosslinking, a form of DNA damage that blocks DNA replication and transcription [5, 6]. The occurrence of DNA damage quickly activates the DDR, a conserved mechanism evolved in eukaryotic cells to govern genomic integrity.

How does cisplatin induced apoptosis?

Cisplatin forms inter- and intrastrand crosslinked DNA adducts and its cytotoxicity is mediated by propagation of DNA damage recognition signals to downstream pathways involving ATR, p53, p73, and mitogen-activated protein kinases, ultimately resulting in apoptosis.

How does cisplatin affect the cell cycle?

Broadly, cisplatin is known to bind DNA and form DNA adducts, which is aimed to subsequently inhibit cell cycle progression and induce apoptosis.

How do cancer cells become resistant to cisplatin?

Inside the tumor cell, decreased drug import, increased drug export, increased drug inactivation by detoxification enzymes, increased DNA damage repair, and inactivated cell death signaling are major mechanisms leading to cisplatin resistance.

How does cisplatin stop DNA replication?

Cisplatin prevents DNA replication in cancer cells by a ligand replacement reaction with DNA in which a bond is formed between platinum and a nitrogen atom on guanine.

Is cisplatin-induced cell death always produced by apoptosis?

In summary, a growing body of evidence suggests that cisplatin-induced cell death does not always come from “classic”apoptosis. Depending on both cisplatin dose and cellular status, cisplatin may also induced cell death by a defective apoptotic program or even by necrosis.

What does cisplatin do to p53?

Cisplatin-induced DNA damage activates p53, which, in turn, transcribes p21 and MDM2, and induces Fas membrane expression. Recently, we have identified the Fas pathway to be involved in cisplatin-induced apoptosis in cisplatin-sensitive TC cell lines.

Is cisplatin an alkylating agent?

Cisplatin, oxaliplatin, carboplatin, chlorambucil, cyclophosphamide, mechlorethamine, and melphalan are some of the most important alkylating agents used for chemotherapy. The exposure of cells to alkylating agents causes a specific reduction in DNA synthesis, chromosomal aberrations, and genetic mutations [15].