Does cisplatin induce apoptosis?

Cisplatin induced an increase in the expression of active caspase-3, indicating cellular apoptosis, and increased the nitration of proteins, 24 h post treatment.

How does cisplatin cause cell death?

In addition, at high doses, cisplatin could damage molecules involved in cellular energy supply (i.e., ATP) and also proteins directly or indirectly involved in the apoptotic process (i.e., p53, Bax, Bcl-2, and caspases), leading to necrotic cell death.

How does cisplatin affect 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 chemotherapy induced apoptosis?

Several reports have suggested that anticancer drugs kill susceptible cells by inducing expression of death receptor ligands, especially Fas ligand (FasL). Other reports have indicated that chemotherapeutic agents trigger apoptosis by inducing release of cytochrome c from mitochondria.

When should you hold cisplatin?

A repeat course of cisplatin (cisplatin injection) should not be given until the serum creatinine is below 1.5 mg/100 mL, and/or the BUN is below 25 mg/100 mL. A repeat course should not be given until circulating blood elements are at an acceptable level (platelets ≥ 100,000/mm3,WBC ≥ 4,000/mm3).

Why does cisplatin cause early 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.

Does chemotherapy induce apoptosis?

Apoptosis has been considered a major mechanism of chemotherapy-induced cell death, and pathways regulating apoptosis are the focus of many preclinical drug discovery investigations.

What chemotherapy drugs cause apoptosis?

Chemotherapeutic Agents Kill Susceptible Cells by Apoptosis

How is cytotoxicity of cisplatin related to 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 is p73 accumulation related to cisplatin treatment?

Thus, cisplatin activates c-Abl, and accumulation of p73 following cisplatin treatment is not observed in c-Abl-defective cells. Cisplatin activation of c-Abl is regulated by MMR because MLH1-defective cells fail to activate c-Abl during cisplatin treatment.

What is the mechanism of resistance to cisplatin?

Cisplatin resistance arises through a multifactorial mechanism involving reduced drug uptake, increased drug inactivation, increased DNA damage repair, and inhibition of transmission of DNA damage recognition signals to the apoptotic pathway.

How is cisplatin used in the treatment of cancer?

Cisplatin is actually one of the most widely used anticancer drugs, and the central role of this drug in human cancer chemotherapy attests to its current importance. Cisplatin-based chemotherapy is highly efficient for the treatment of patients with a variety of cancers such as lung, ovarian, head and neck, and gastric cancer [ 3