How does etoposide cause apoptosis?
Low or high concentrations of etoposide have different effects on transcriptional regulation by p53. Tumor suppressor protein p53 plays an important role in DNA damage-induced apoptosis, at least partly by acting as a transcription factor to direct the expression of apoptotic mediators.
Do HeLa cells undergo apoptosis?
In conclusion, like full-length wild-type p53, overex- pressed p53d1214 induces a typical apoptotic response in transfected HeLa cells. The results obtained with p53d1214 argued that, at least in HeLa cells, p53-mediated apoptosis can occur in the absence of SST.
What does etoposide do to cells?
Etoposide kills cells by stabilizing a covalent enzyme-cleaved DNA complex (known as the cleavage complex) that is a transient intermediate in the catalytic cycle of topoisomerase II.
What is the mechanism of action of etoposide?
Etoposide (VP-16). Its mechanism of action is to cause single-strand and double-strand breaks in DNA through interaction with DNA topoisomerase II, inducing arrest in the G2-phase of the cell cycle [8,21,154]. This activity is mediated through the formation of a stable complex with DNA and topoisomerase II.
How does apoptosis relate to HeLa cells?
Apoptosis is the primary mode of HeLa cell death in our system, and apoptosis occurs in a manner dependent on concentration, irradiation dose, and drug–light intervals. After endocytosis mediated by the folate receptor, PS I was primarily localized to the mitochondria and the endoplasmic reticulum (ER) of HeLa cells.
How long does etoposide stay in the body?
On intravenous administration, the disposition of Etoposide is best described as a biphasic process with a distribution half-life of about 1.5 hours and terminal elimination half-life ranging from 4 to 11 hours.
What class of drugs is etoposide?
Etoposide is in a class of medications known as podophyllotoxin derivatives. It works by slowing or stopping the growth of cancer cells in your body.
Do you lose your hair with etoposide?
This medicine often causes a temporary loss of hair. After treatment with etoposide has ended, normal hair growth should return.
How does PFT-α affect etoposide induced apoptosis?
Effect of PFT-α on etoposide-induced apoptosis. a MEFs, pre-treated with 30 μM PFT-α followed by 18 h treatment with 1.5, 15 or 150 µM etoposide, were analyzed by flow cytometry to determine percentage of cells having sub-G1 DNA content. Cells were treated in parallel with UVC and analyzed after 18 h. Control indicates normally proliferating cells.
How is etoposide used in the treatment of cancer?
Etoposide has been used clinically in cancer treatment, as well as in numerous research studies, for many years. However, there is incomplete information about its exact mechanism of action in induction of cell death. Etoposide was compared at various concentrations to characterize the mechanisms by which it induces cell death.
How does etoposide affect the function of p53?
Here we demonstrate that treatment of MEFs with higher concentrations of etoposide induce apoptosis and activate the transcription-dependent functions of p53. Interestingly, lower concentrations of etoposide also induced apoptosis, but without any evidence of p53-dependent transcription up-regulation.
Where does etoposide accumulate in the cell cycle?
Etoposide-treated cells accumulate at G2/M, which can occur in both p53-dependent and -independent pathways [ 16 ]. In the p53-independent pathway the cell cycle block induced by DNA damage is controlled by ATM/ATR protein kinases.