What does doxorubicin do to the cell cycle?
Doxorubicin (DOX) is involved in the induction of DNA damage, inhibition of cell proliferation, impairment of mitochondria, and cell death.
How does doxorubicin work on cancer cells?
Doxorubicin is a type of chemotherapy drug called an anthracycline. It slows or stops the growth of cancer cells by blocking an enzyme called topo isomerase 2. Cancer cells need this enzyme to divide and grow. You might have doxorubicin in combination with other chemotherapy drugs.
Does doxorubicin induced apoptosis?
Doxorubicin induces apoptosis via the activation of caspases and disruption of mitochondrial membrane potential (Gamen et al., 2000). Despite the widespread clinical use of doxorubicin, its antiproliferative and death-inducing signal cascades are not yet fully understood.
What is the mechanism of action of doxorubicin at the molecular level?
There are two proposed mechanisms by which doxorubicin acts in the cancer cell (i) intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair and (ii) generation of free radicals and their damage to cellular membranes, DNA and proteins (shown in Fig.
What is the IC50 of doxorubicin?
Among these breast cancer cell lines, the T47D cell line exhibited low sensitivity to doxorubicin, with a IC50 value of 8.53 µM (Fig. 1i).
What is doxorubicin induced cardiomyopathy?
Doxorubicin (Dox) is a highly effective anticancer drug but cause acute ventricular dysfunction, and also induce late-onset cardiomyopathy and heart failure. Despite extensive studies, the pathogenic sequelae leading to the progression of Dox-associated cardiomyopathy remains unknown.
Is doxorubicin a neurotoxic?
Doxorubicin causes neurotoxicity by facilitating ROS production and mitochondrial membrane depolarization in neurons (19, 22). Doxorubicin increases the MOMP and Bax/Bcl-2 ratio, leading to mitochondrial degeneration and neuronal dysfunction (19, 24).
What is the enzyme responsible for Methylating DNA?
DNMT1, the major enzyme involved in DNA methylation inheritance. DNMT1, a large protein of 1616 amino acids (aa) which mainly catalyzes DNA methylation inheritance activity, is composed of a large regulator N-terminal region (1000 aa) and a small catalytic C-terminal region.
How does doxorubicin cause dilated cardiomyopathy?
Doxorubicin appears to induce toxic damage to the mitochondria of cardiomyocytes. Several mitochondrial enzymes such as NADH dehydrogenase, cytochrome P-450 reductase and xanthine oxidase are involved in generating oxygen free radicals (reactive oxygen species) [3,23,24,25].
How does doxorubicin cause heart failure?
This increase in endothelin-1 caused by doxorubicin potentiates the increased calcium load in cardiomyocytes, thereby facilitating apoptosis and cardiac dysfunction. Clinically, patients with doxorubicin-induced congestive heart failure also have increased levels of endothelin-1.
How is doxorubicin metabolism?
The currently known metabolism of doxorubicin is mainly mediated by the cytochrome P450. in addition, carbonyl reductase and aldo-keto reductase have also been shown to be involved in some metabolic processes. But none of these enzymes catalyze metabolic reactions to get these newly discovered metabolites.
Does doxorubicin cross the blood brain barrier?
(A) Doxorubicin can cross the blood-brain barrier through vascular-associated apical projections of neural stem cells.
What is the difference between Ki and IC50?
The value Ki is the dissociation constant describing the binding affinity between the inhibitor and the enzyme, while IC50 is the concentration of inhibitor required to reduce the enzymatic activity to half of the uninhibited value. Both values can be used as quantitative indexes for the inhibitor potency.
What is positive control in PCR?
Positive PCR Control (PPC) is used to test for the presence of inhibitors in the sample or the efficiency of the polymerase chain reaction itself using a pre-dispensed artificial DNA sequence and the primer set that detects it.