Does gemcitabine induce apoptosis?

Gemcitabine can induce apoptosis in cancer cells through GSK-3β and PAP inhibition, and TP53INP1 and GSK-3βser9 activation.

Does cisplatin induced apoptosis?

Cisplatin induces apoptosis in auditory, renal, and neuronal cells. Treatment of UBOC1, HK2, and SH-SY5Y cells with 10, 20, and 5 μM of cisplatin, respectively, increased the expression of activated caspase-3, a biomarker of apoptosis, 24 h post treatment (Figure 1).

How does gemcitabine cause apoptosis?

Gemcitabine also inhibits DNA synthesis indirectly by decreasing cellular dNTP pools via inhibition of ribonucleotide reductase. Incubation of human leukemia cells (CEM) with gemcitabine leads to apoptotic cell death.

How does cisplatin cause cellular 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 does cisplatin do to 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.

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.

What is the mechanism of action of gemcitabine?

The most important mechanism of action of gemcitabine is inhibition of DNA synthesis (Huang et al., 1991). When dFdCTP is incorporated into DNA, a single deoxynucleotide is incorporated afterwards, preventing chain elongation (Gandhi et al., 1996).

Does gemcitabine inhibit DNA polymerase?

Gemcitabine inhibits DNA synthesis by intracellular conversion by deoxycytidine kinase to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides that lead to competitive inhibition of DNA polymerase.

Does cisplatin damage healthy cells?

Cisplatin damages the DNA inside the cancer cells and so prevents them from multiplying. Unfortunately, cisplatin can also affect normal, healthy cells, particularly those that multiply quickly, such as blood cells and hair cells. The most important side effect is on the bone marrow where blood cells are made.

Does cisplatin increase p53 expression?

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.

What is cisplatin which type of apoptotic pathway can it activate?

Accumulating evidence has shown that cisplatin activates the p53-dependent apoptotic pathway, but it also induces apoptosis in p53-mutated cancer cells.

How does gemcitabine and cisplatin work?

How does gemcitabine + cisplatin work? Each of the medications in the gemcitabine and cisplatin (also known as gem/cis) regimen are designed to kill or slow growth of bladder cancer cells. Goals of therapy: Cisplatin plus gemcitabine is given to shrink bladder tumors and decrease symptoms from bladder cancer.

How does gemcitabine stop DNA replication?

How long can you take gemcitabine and cisplatin?

You usually have GC chemotherapy as cycles of treatment. Each cycle takes 3 weeks. You usually have between 4 to 6 cycles of treatment taking from 3 to 6 months.

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.