Enhanced anticancer efficacy of α-tocopheryl succinate by conjugation with polyethylene glycol
Drug Carriers
Dose-Response Relationship, Drug
Molecular Structure
Cell Survival
Injections, Subcutaneous
Immunoblotting
Drug Evaluation, Preclinical
Mice, Nude
Antineoplastic Agents
Apoptosis
02 engineering and technology
Flow Cytometry
Polyethylene Glycols
3. Good health
Kinetics
Mice
Cell Line, Tumor
Animals
Humans
Female
Reactive Oxygen Species
0210 nano-technology
Neoplasm Transplantation
DOI:
10.1016/j.jconrel.2005.05.014
Publication Date:
2005-08-03T23:13:47Z
AUTHORS (8)
ABSTRACT
Alpha-tocopheryl polyethylene glycol succinate (TPGS) has been used to enhance the bioavailability of poorly absorbed drugs and as a vehicle for drug delivery systems. In response to recent reports that alpha-tocopheryl succinate (TOS) acts as an anticancer agent, we investigated whether its polyethylene glycol (PEG) conjugate, TPGS, also possesses anticancer activity. TPGS inhibited the growth of human lung carcinoma cells implanted in nude mice, and in an in vitro cell culture, even more potently than TOS. The time-dependent uptake of TPGS into cells did not differ from that of TOS, indicating that the enhanced antitumor efficacy of TPGS was not due to its increased uptake into cells. Compared with TOS, TPGS was more effective at inducing apoptosis and the generation of reactive oxygen species, suggesting that the superior anticancer efficacy of TPGS is associated with its increased ability to induce apoptosis. Our data suggest that further studies assessing the potential usefulness of TPGS in cancer therapeutics are warranted, since its use as a vehicle in the formulation of anticancer drugs may provide an effective way to improve their therapeutic efficacy.
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