PEGylated conjugated linoleic acid stimulation of apoptosis via a p53-mediated signaling pathway in MCF-7 breast cancer cells

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 70; no. 2; pp. 621 - 626
• Main Authors: Seo, Ji-Hye, Moon, Hyun-Seuk, Kim, In-Yong, Guo, Ding-Ding, Lee, Hong-Gu, Choi, Yun-Jaie, Cho, Chong-Su
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.10.2008; Elsevier Science
• Subjects: Animals; Anti-cancer; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Cycle - drug effects; Cell Line, Tumor; Conjugated linoleic acid (CLA); General pharmacology; Half-Life; Humans; Linoleic Acids, Conjugated - chemistry; Linoleic Acids, Conjugated - pharmacology; Medical sciences; Mice; Nanoparticle; NIH 3T3 Cells; PEGylation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly (ethylene glycol) (PEG); Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacology; Pro-drug; Prodrugs - pharmacology; Signal Transduction - physiology; Tumor Suppressor Protein p53 - physiology; PEGylation; Anti-cancer; Poly (ethylene glycol) (PEG); Nanoparticle; Conjugated linoleic acid (CLA); Pro-drug; Antineoplastic agent; Conjugated linoleic acid; Breast disease; Pharmaceutical technology; Breast cancer; Malignant tumor; Prodrug; Ethylene oxide polymer; Mammary gland diseases; Signal transduction; TP53 Gene; Cell death; Microparticle; Pegylated form; Tumor cell; Cancer; Apoptosis; Tumor suppressor gene
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2008.05.009

The objective of this study was to investigate whether PEGylated conjugated linoleic acid (PCLA), as compared with conjugated linoleic acid (CLA) alone, displays anti-cancer properties in MCF-7 breast cancer cells. To generate PCLA, CLA was simply coupled to poly(ethylene glycol) (PEG) at the melting state of PEG without a solvent or a catalyst. The coupling reaction generated an ester linkage between the carboxyl group of CLA and hydroxyl one of PEG. The half-life of the generated PCLA was 52 h at pH 7.4 at 37 °C, indicating that PCLA potentially acts as a pro-drug. Apoptosis of MCF-7 breast cancer cells treated with PCLA showed a dose response to PCLA concentration during treatment. In addition, pro-apoptotic proteins such as Bax were up-regulated, whereas anti-apoptotic proteins, such as Bcl-2, were down-regulated by treatment with both CLA and PCLA. The tumor suppressor gene p53 was significantly up-regulated by treatment with increasing concentrations of PCLA, suggesting that PCLA-induced apoptosis is regulated by a p53-mediated signaling pathway. Overall, the anti-cancer effects of PCLA on MCF-7 breast cancer cells may have therapeutic significance.