PEGylated conjugated linoleic acid stimulation of apoptosis via a p53-mediated signaling pathway in MCF-7 breast cancer cells.
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 52h at pH 7.4 at 37 degrees 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.
Seo
Ji-Hye
JH
School of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.
Moon
Hyun-Seuk
HS
Kim
In-Yong
IY
Guo
Ding-Ding
DD
Lee
Hong-Gu
HG
Choi
Yun-Jaie
YJ
Cho
Chong-Su
CS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006207:Half-Life; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000970:Antineoplastic Agents; D044243:Linoleic Acids, Conjugated; D011355:Prodrugs; D016159:Tumor Suppressor Protein p53; D011092:Polyethylene Glycols