Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells.
BACKGROUND
Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent employed today and is nontoxic to humans at high levels (50 microg/ml). Clinically relevant concentrations of propofol (3 to 8 microg/ml; 20 to 50 microM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA).


METHODS
The conjugates linking an omega-3 fatty acid, either DHA or EPA, with propofol were synthesized and tested for their effects on migration, adhesion and apoptosis on MDA-MB-231 breast cancer cells.


RESULTS
At low concentrations (25 microM), DHA, EPA or propofol alone or in combination had minimal effect on cell adhesion to vitronectin, cell migration against serum and the induction of apoptosis (only 5 to 15% of the cells became apoptotic). In contrast, the propofol-DHA or propofol-EPA conjugates significantly inhibited cell adhesion (15 to 30%) and migration (about 50%) and induced apoptosis (about 40%) in breast cancer cells.


CONCLUSIONS
These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer.
Siddiqui
Rafat A
RA
Methodist Research Institute, Clarian Health Partners, Indianapolis, IN, USA. rsiddiqu@clarian.org
Zerouga
Mustapha
M
Wu
Min
M
Castillo
Alicia
A
Harvey
Kevin
K
Zaloga
Gary P
GP
Stillwell
William
W
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000633:toxicity*; D015118:Eicosapentaenoic Acid / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D015742:Propofol / Q000633:toxicity*
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D020169:Caspases; D015742:Propofol