Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0029463 (
osteosarcoma
)
16,637
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
2 mM
Ascorbic acid
has a potent cytotoxic effect on neuroblastoma,
osteosarcoma
, retinoblastoma, and rhabdomyosarcoma cells cultured in vitro. At a lower concentration (0.2 mM), ascorbic acid remains highly cytotoxic for neuroblastoma,
osteosarcoma
and retinoblastoma cells, but it has a stimulatory effect on the growth of rhabdomyosarcoma cells.
...
PMID:Ascorbic acid is cytotoxic for pediatric tumor cells cultured in vitro. 770 4
Background:
High-dose, pharmacological ascorbate (P-AscH
-
) is preferentially cytotoxic to human cancer cells
in vitro
. Investigations on the efficacy of P-AscH
-
as an adjuvant treatment for multiple human cancers are on-going, but has yet to be formally investigated in dogs. The primary objectives of this study were to determine the pharmacokinetic (PK) profile of P-AscH
-
in healthy Beagle dogs and the effects of P-AscH
-
on canine
osteosarcoma
cells
in vitro
.
Methods:
Eight purpose-bred, healthy, spayed female Beagle dogs, between 20 and 21 months old, and 8-10 kg were administered two doses of P-AscH
-
(550 or 2,200 mg/kg)
via
intravenous infusion over 6 h, on separate days. Plasma ascorbate concentrations were measured at 12 time points during and after infusion for PK analysis using nonlinear mixed-effects (NLME) and non-compartmental analysis (NCA). Clonogenic assays were performed on 2 canine
osteosarcoma
cell lines (D-17 and OSCA-8) and canine primary dermal fibroblasts after exposure to high concentrations of ascorbate (75 pmoles/cell).
Results:
Plasma ascorbate levels in the dogs peaked at approximately 10 mM following 2,200 mg/kg and returned to baseline 6-8 h after dosing. Minor adverse effects were seen in two dogs.
Ascorbate
(75 pmoles/cell) significantly decreased survival in both the
osteosarcoma
cell lines (D-17 63% SD 0.010,
P
= 0.005; OSCA-8 50% SD 0.086,
P
= 0.026), compared to normal fibroblasts (27% SD 0.056).
Conclusions:
Pharmacological ascorbate is preferentially cytotoxic to canine-derived cancer cells. High levels of ascorbate can be safely administered to dogs. Further studies are needed to determine the effects of P-AscH
-
on canine patients.
...
PMID:
In vitro
Cytotoxicity and Pharmacokinetic Evaluation of Pharmacological Ascorbate in Dogs. 3178 83
Vitamin C
and iron are both important nutrients for humans and involved in several physiological processes. The biological activities of vitamin C and iron are based on their abilities to accept or donate electrons. Although vitamin C is well known as an excellent electron donor in physiological conditions, it also has pro-oxidant properties, especially with catalytic metal iron. Cancer cells have a higher iron requirement than normal cells, which allows pharmacological ascorbate to kill cancer cells selectively. In this study, we demonstrated that the levels of H
2
O
2
in cells were significantly raised after treated with pharmacological ascorbate, and intracellular labile iron could increase pharmacological ascorbate-mediated oxidative stress by Fenton reaction. Catalytic metal iron plays opposite roles in and outside cells. Intracellular excess labile iron improved ascorbate-induced toxicity, while the excess labile iron in the medium abolished ascorbate-induced toxicity. Fe
3+
and Fe
2+
have the same effect on ascorbate-induced toxicity, but Fe
3+
chelator deferoxamine (DFO) has a profound inhibition effect than Fe
2+
chelator 2,2'-bipyridyl (BIP) on ascorbate-induced toxicity. The influence of intracellular labile iron and ascorbate on the ferritin expression may cause selective sensitivity in
osteosarcoma
cell lines on pharmacological ascorbate. High iron requirement of many cancer cells facilitates pharmacological ascorbate on cancer treatment. In addition, increasing iron content in tumour tissue may be effective strategies to improve the effects of pharmacological ascorbate.
...
PMID:Labile iron affects pharmacological ascorbate-induced toxicity in osteosarcoma cell lines. 3218 98
