Research Shows the Role of Polyphenols in Inhibiting Cancer Metastasis

Scientists from the Biomedical Research Institute of Málaga and the Nanomedicine Platform have pub­lished a study explor­ing the role of oleo­can­thal and olea­cein in mod­u­lat­ing angio­gen­e­sis, the for­ma­tion of new blood ves­sels, which is directly related to the pro­gres­sion of dif­fer­ent types of tumors and the metas­ta­sis of can­cer.

Oleocanthal and olea­cein, sec­oiri­doid-related phe­no­lic com­pounds, are found in extra vir­gin olive oil. Both com­pounds are known for their antiox­i­dant and anti-inflam­ma­tory prop­er­ties and have been the sub­ject of much sci­en­tific inves­ti­ga­tion.

However, prior research into their effects on angio­gen­e­sis was lim­ited. The new study seeks to address this gap by explor­ing the anti-angio­genic prop­er­ties of the com­pounds, both in vitro and in vivo.

Angiogenesis, the growth of new blood ves­sels from exist­ing ones, is cru­cial for solid tumor growth and sur­vival.

Tumor angio­gen­e­sis involves the devel­op­ment of blood ves­sels into the can­cer­ous mass to sup­ply nutri­ents and oxy­gen, sup­port­ing tumor growth and metas­ta­sis. Angiogenesis inhibitors are con­sid­ered a means of com­ple­ment­ing other ther­a­pies and pre­vent­ing malig­nant tumor devel­op­ment.

Anti-angio­genic ther­apy, while not a cure, is effec­tive in destroy­ing tumors because vas­cu­lar sup­ply is essen­tial for their growth.

This approach con­fers cer­tain advan­tages com­pared to non-spe­cific meth­ods, such as chemother­apy and radio­ther­apy, by reduc­ing tox­i­c­ity and drug resis­tance and pro­vid­ing a less toxic, long-term tumor treat­ment.

Angiogenesis involves sev­eral stages, and dis­rupt­ing any one step can thwart the process. Oleacein and oleo­can­thal were found to inhibit endothe­lial cell (the cells that line the inter­nal walls of blood ves­sels) inva­sion, cor­re­lat­ing with a decrease in MMP‑2 activ­ity, an enzyme that degrades the extra­cel­lu­lar matrix, which is cru­cial dur­ing angio­gen­e­sis.

Through a test involv­ing the for­ma­tion of blood ves­sel-like struc­tures on Matrigel, the researchers showed that olea­cein and oleo­can­thal inter­fere with the for­ma­tion of tubu­lar struc­tures by endothe­lial cells in a dose-depen­dent man­ner. Even at low micro­mo­lar doses (non-toxic for such cells), the inhi­bi­tion exceeded 50 per­cent.

Notably, these com­pounds did not affect pre-exist­ing tubu­lar struc­tures, imply­ing that they dis­rupt the for­ma­tion of new ves­sels via angio­gen­e­sis with­out affect­ing estab­lished ones. This fea­ture makes them more suit­able as anti-angio­genic drugs are safer for exist­ing, well-estab­lished blood ves­sels.

The results sug­gest the poten­tial of oleo­can­thal and, par­tic­u­larly, olea­cein as anti-angio­genic agents.

The researchers believe that while fur­ther pre-clin­i­cal and clin­i­cal stud­ies are war­ranted, these find­ings open new avenues for research into devel­op­ing ther­a­peu­tic strate­gies involv­ing these nat­ural com­pounds.

They also believe that the poten­tial ben­e­fits of olea­cein and oleo­can­thal extend beyond can­cer ther­apy, mak­ing them intrigu­ing can­di­dates for address­ing many angio­gen­e­sis-related health con­cerns such as pso­ri­a­sis, arthri­tis, blind­ness and numer­ous rare dis­eases.

“Oleacein and oleo­can­thal have been pro­posed as good can­di­dates for angio­pre­ven­tion and as a basis for future stud­ies mod­u­lat­ing angio­gen­e­sis in clin­i­cal inter­ven­tions, as well as func­tional claims of inter­est to the food indus­try for their health ben­e­fits,” said Ana Dacil, the study’s lead author.

She also noted that this is attrac­tive to the indus­try com­mer­cially due to the grow­ing aware­ness of extra vir­gin olive oil as a func­tional food.

“This type of study rein­forces the health ben­e­fits of extra vir­gin olive oil, mak­ing it one of the main foods that sus­tain our Mediterranean diet and help­ing in the pre­ven­tion and devel­op­ment of var­i­ous dis­eases,” said Miguel Angel Medina, a pro­fes­sor of bio­chem­istry and mol­e­c­u­lar biol­ogy at the University of Málaga.

While the con­cen­tra­tion of phe­no­lic com­pounds in extra vir­gin olive oil varies accord­ing to sev­eral fac­tors, such as the region of ori­gin, the olive cul­ti­var, the stage of fruit ripen­ing, and the extrac­tion process, the aver­age daily con­sump­tion of 40 mil­li­liters (approx­i­mately four table­spoons) of high-qual­ity extra vir­gin olive oil con­tains a min­i­mum of 10 mil­ligrams of olea­cein and around 25 mil­ligrams of oleo­can­thal.

Oleocanthal, respon­si­ble for many of the spicy and bit­ter notes of high-qual­ity oils, has anti-inflam­ma­tory prop­er­ties and anti-car­cino­genic poten­tial, and has been shown to con­fer pro­tec­tion against var­i­ous neu­rode­gen­er­a­tive dis­eases such as Alzheimer’s.

Oleacein, for its part, pos­sesses antiox­ida­tive, hypoten­sive and anti-inflam­ma­tory prop­er­ties. The polyphe­nol has shown ben­e­fi­cial activ­ity on the car­dio­vas­cu­lar sys­tem. Studies have sug­gested that the com­pound may even aid the body in repair­ing tis­sues dam­aged by infarc­tion – tis­sue death due to inad­e­quate blood sup­ply.