Study Reveals Therapeutic Properties of EVOO Polyphenols on Childhood Cancer

A joint study car­ried out by researchers from the uni­ver­si­ties of Castilla-La Mancha, Porto, Lisbon and Palermo has ana­lyzed the ther­a­peu­tic poten­tial of oleu­ropein and hydrox­y­ty­rosol in treat­ing neu­rob­las­toma, a can­cer affect­ing young chil­dren.

The review empha­sizes the role of the Mediterranean diet and olive oil, which con­tain both polyphe­nols, under­scor­ing their antiox­i­dant prop­er­ties, which could bol­ster cel­lu­lar defenses and mit­i­gate oxida­tive dam­age in neu­rob­las­toma cells.

Additionally, oleu­ropein and hydrox­y­ty­rosol are shown to induce apop­to­sis (cell death), reduce side effects from con­ven­tional treat­ments and coun­ter­act tumor dor­mancy as a resis­tance mech­a­nism, sug­gest­ing promis­ing avenues for future research, espe­cially in vivo stud­ies.

Neuroblastoma is a chal­leng­ing pedi­atric can­cer that pri­mar­ily affects chil­dren aged 17 to 18 months. It arises from neural crest cells of the sym­pa­thetic ner­vous sys­tem and com­monly orig­i­nates in the adrenal glands, neck, chest or spinal cord.

Despite advances in treat­ment modal­i­ties such as chemother­apy, surgery and radio­ther­apy, neu­rob­las­toma remains a for­mi­da­ble clin­i­cal entity due to its propen­sity for recur­rence and the devel­op­ment of drug resis­tance. Therefore, there is an urgent need for novel ther­a­peu­tic strate­gies to improve out­comes for patients.

The review under­scored the poten­tial of nat­ural com­pounds derived from the Mediterranean diet in address­ing the ther­a­peu­tic chal­lenges of neu­rob­las­toma. Their acces­si­bil­ity and reduced cyto­tox­i­c­ity make them attrac­tive can­di­dates for inte­gra­tion with con­ven­tional treat­ments.

For exam­ple, gar­lic-derived com­pounds and antiox­i­dants from red wine have shown anti­cancer effects in var­i­ous can­cer types, includ­ing neu­rob­las­toma. Leveraging these nat­ural sub­stances to enhance treat­ment effi­cacy and mit­i­gate side effects holds promise, par­tic­u­larly in pedi­atric oncol­ogy.

The Mediterranean diet is renowned for its health ben­e­fits and pro­tec­tive effects against var­i­ous dis­eases, includ­ing can­cer.

Extra vir­gin olive oil, the pri­mary source of fat in the Mediterranean diet, con­tains bioac­tive phe­no­lic com­pounds, includ­ing oleu­ropein and hydrox­y­ty­rosol, which have gar­nered sci­en­tific inter­est for their antiox­i­dant, anti-inflam­ma­tory and anti­cancer prop­er­ties.

Oleuropein, the prin­ci­pal phe­no­lic com­pound found in olive oil, demon­strates diverse ther­a­peu­tic poten­tials, includ­ing car­dio­pro­tec­tive, anti-inflam­ma­tory and neu­ro­pro­tec­tive effects. Its abil­ity to inter­act with crit­i­cal mol­e­c­u­lar path­ways in dis­ease pro­gres­sion makes it an attrac­tive can­di­date for can­cer ther­apy.

Upon hydrol­y­sis, oleu­ropein yields hydrox­y­ty­rosol, which shares sim­i­lar ben­e­fi­cial prop­er­ties and has been shown to exert potent anti­cancer effects in var­i­ous tumor types.

One of can­cer cells’ hall­mark fea­tures is their dys­reg­u­lated redox bal­ance, which leads to increased pro­duc­tion of reac­tive oxy­gen species (ROS) and oxida­tive stress.

With their antiox­i­dant prop­er­ties, Oleuropein and hydrox­y­ty­rosol can poten­tially mit­i­gate oxida­tive dam­age and bol­ster cel­lu­lar antiox­i­dant defenses in neu­rob­las­toma cells.

By scav­eng­ing free rad­i­cals and mod­u­lat­ing oxida­tive stress path­ways, these phe­no­lic com­pounds may inhibit tumor growth, induce apop­to­sis and sen­si­tize tumor cells to con­ven­tional treat­ments.

In addi­tion to their antiox­i­dant effects, oleu­ropein and hydrox­y­ty­rosol have been shown to mod­u­late var­i­ous sig­nal­ing path­ways involved in can­cer pro­gres­sion.

They can inhibit nuclear fac­tor kappa-light-chain-enhancer of acti­vated B cells (NF-κB) acti­va­tion, hypoxia-inducible fac­tor 1α (HIF-1α) expres­sion and his­tone deacety­lase (HDAC) activ­ity, thereby sup­press­ing inflam­ma­tory responses, angio­gen­e­sis and tumori­ge­n­e­sis.

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.

The review high­lighted the impor­tance of explor­ing the phar­ma­co­ki­net­ics and bioavail­abil­ity of oleu­ropein and hydrox­y­ty­rosol to opti­mize their ther­a­peu­tic effi­cacy.

Despite their low bioavail­abil­ity, these com­pounds can reach ther­a­peu­tic con­cen­tra­tions in tar­get tis­sues, par­tic­u­larly in tumors, due to their abil­ity to cross the blood-brain bar­rier and inter­act with cel­lu­lar tar­gets.

The researchers indi­cated that strate­gies to enhance the deliv­ery and bioavail­abil­ity of oleu­ropein and hydrox­y­ty­rosol, such as nanofor­mu­la­tions and tar­geted drug deliv­ery sys­tems, war­rant fur­ther inves­ti­ga­tion to max­i­mize their clin­i­cal util­ity in neu­rob­las­toma treat­ment.

Moreover, oleu­ropein and hydrox­y­ty­rosol exhibit selec­tive cyto­tox­i­c­ity towards can­cer cells while spar­ing nor­mal cells, mak­ing them promis­ing can­di­dates for tar­geted can­cer ther­apy.

Preclinical stud­ies have demon­strated promis­ing results, includ­ing inhi­bi­tion of tumor growth, induc­tion of apop­to­sis and sen­si­ti­za­tion of tumor cells to chemother­apy.

However, the researchers added that trans­lat­ing these find­ings into clin­i­cal prac­tice requires rig­or­ous eval­u­a­tion in well-designed clin­i­cal tri­als to estab­lish safety, effi­cacy and opti­mal dos­ing reg­i­mens.

The authors note that fur­ther research is needed to fully elu­ci­date their mech­a­nisms of action, opti­mize their phar­ma­co­ki­net­ics and eval­u­ate their clin­i­cal effi­cacy in neu­rob­las­toma patients.

By har­ness­ing the ther­a­peu­tic poten­tial of oleu­ropein and hydrox­y­ty­rosol, they hope to pave the way for more effec­tive and less toxic treat­ments for neu­rob­las­toma and other pedi­atric can­cers, ulti­mately improv­ing out­comes and qual­ity of life for affected patients and their fam­i­lies.