Enhanced anticancer efficacy of α-tocopheryl succinate by conjugation with polyethylene glycol

• Published in: Journal of controlled release Vol. 107; no. 1; pp. 43 - 52
• Main Authors: Youk, Hee-Jeong, Lee, Eunmyong, Choi, Moon-Kyung, Lee, Young-Ju, Chung, Jun Ho, Kim, So-Hee, Lee, Chang-Hun, Lim, Soo-Jeong
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20.09.2005; Elsevier
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cancer; Cell Line, Tumor; Cell Survival - drug effects; Conjugation; Dose-Response Relationship, Drug; Drug Carriers; Drug Evaluation, Preclinical; Female; Flow Cytometry; General pharmacology; Humans; Immunoblotting; Injections, Subcutaneous; Kinetics; Medical sciences; Mice; Mice, Nude; Molecular Structure; Neoplasm Transplantation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene glycol; Polyethylene Glycols - chemistry; Polyethylene Glycols - metabolism; Polyethylene Glycols - pharmacology; Reactive Oxygen Species - metabolism; Transplantation, Heterologous; Vitamin E - analogs & derivatives; Vitamin E - chemistry; Vitamin E - metabolism; Vitamin E - pharmacology; Xenograft Model Antitumor Assays; α-tocopheryl succinate; PEG; Polyethylene glycol; ROS; TOS; PARP; Conjugation; DCFH; TPGS; α-tocopheryl succinate; Apoptosis; Cancer; Antineoplastic agent; Ethylene oxide polymer; Pharmaceutical technology; Cell death; Malignant tumor
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2005.05.014

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.