How does cisplatin cause 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.
What is cisplatin which type of apoptotic pathway can it activate?
Our results indicate that cisplatin induces apoptosis in cultured proximal tubule cells via activation of a mitochondrial signaling pathway.
What is the mechanism of action of cisplatin?
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, and/or DNA replication mechanisms.
How does cisplatin act as anticancer?
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.
What does cisplatin do to p53?
Following cisplatin exposure, expression levels of p53 increased, with a subsequent increase in MDM2 and p21 mRNA and protein levels and Fas cell membrane levels. Downregulation of p53 with siRNA lowered cisplatin-induced apoptosis in Tera and Tera-CP, which was associated with a diminished Fas membrane expression.
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.
What is the mode of cytotoxic action of cisplatin?
Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, primarily intrastrand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis.
What is the half life of cisplatin?
It has a melting point of 207° C. with a terminal half-life of 36 to 47 days. platinum is excreted beyond 24 hours post-infusion and most of the platinum excreted in the urine in 24 hours is excreted within the first few hours.
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.
How does cisplatin enter cells?
This supports the hypothesis that cisplatin can enter cells via passive permeation through the lipid phase of the membrane, but becomes trapped within the cytoplasm because dissociation of chloride ligands yields a membrane-impermeant positively-charged aqua derivative.
Why is cisplatin so 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.
What are the long term effects of cisplatin?
Cisplatin (CDDP) is a frequently employed chemotherapeutic drug both in curative and palliative settings. When cancer patients are cured due to CDDP therapy, they unfortunately often experience severe long‐term side effects including irreversible hearing loss (ototoxicity) and permanent neuronal and renal damage.
Does cisplatin ever leave your body?
Cisplatin is cleared from your body through the kidneys. The kidney’s filtering process prevents the drug from staying in your body too long and causing excessive damage to the normal cells.
What process does cisplatin stop?
The Pt(II) complex cisplatin is used as an anticancer drug. 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.
How is cisplatin metabolized?
A small amount of cisplatin is excreted via the bile and saliva (McEvoy, 1992). After a dose of cisplatin: 15 to 30% of the dose is excreted in the urine in the first 2 to 4 hours (of which 90% is intact cisplatin) 20 to 80% of the dose is recovered in the first 24 hours (NDIS, 1985).
What is the antidote for cisplatin?
No specific antidote for cisplatin exists. Key management principles and strategies to lessen toxicities include renoprotection and enhancing drug elimination with aggressive intravenous hydration with or without the use of an osmotic diuretic, and avoidance of nephrotoxic medications.
What organs does cisplatin affect?
Cisplatin (cis- diamminedichloroplatinum(II), CDDP) is an antineoplastic drug used in the treatment of many solid-organ cancers, including those of the head, neck, lung, testis, ovary, and breast.
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Table 1.
| Acute kidney injury (20–30%) | [15,16] |
|---|---|
| Chronic renal failure | [15,45,46] |
How long does cisplatin chemo stay in your body?
It generally takes about 48 to 72 hours for your body to break down and/or get rid of most chemo drugs.
How many cycles of cisplatin can you have?
You usually have between 4 to 6 cycles of treatment taking from 3 to 6 months.
How can I flush chemo out of my system?
Drinking plenty of water before and after treatment helps your body process chemotherapy drugs and flush the excess out of your system.
What does cisplatin do in the body?
Cisplatin injection is used to treat advanced cancer of the bladder, ovaries, or testicles. Cisplatin is an antineoplastic agent (cancer medicine). It interferes with the growth of cancer cells, which are eventually destroyed by the body. This medicine is to be given only by or under the direct supervision of a doctor.
What is the half-life of cisplatin?
How poisonous is cisplatin?
The major toxicities of a cisplatin overdose include nausea and vomiting, renal insufficiency, electrolyte abnormalities, myelosuppression, ototoxicity, peripheral neuropathy, hepatotoxicity and retinopathy. Diarrhoea, pancreatitis, seizures and respiratory failure have also been reported.
Does drinking water help flush out chemo?
Chemotherapy can be dehydrating. Drinking plenty of water before and after treatment helps your body process chemotherapy drugs and flush the excess out of your system.
Is there a lifetime limit on chemotherapy?
You can have chemo more than once in your lifetime, its Radiation that you can only have once in your lifetime in whichever area was radiated. A MyBCTeam Member said: Chemo is really a catch 22, it does kill the cancer but it is a battle on your body.