Exploring olive oil compounds oleuropein and hydroxytyrosol as potential treatments for neuroblastoma

By Vijay Kumar MalesuReviewed by Lily Ramsey, LLMMar 15 2024

In a recent review published in the Nutrients, a group of authors explored the therapeutic potential of oleuropein (OLE) and hydroxytyrosol (HT) from olive oil as novel antioxidants in the treatment of neuroblastoma (NB), addressing challenges such as recurrence and drug resistance.

Study: Olive Oil Components as Novel Antioxidants in Neuroblastoma Treatment: Exploring the Therapeutic Potential of Oleuropein and Hydroxytyrosol. Image Credit: DUSAN ZIDAR/Shutterstock.com

Background 

NB, the most common extracranial tumor in young children, originates from nerve tissues and is challenging due to recurrence and drug resistance.

Olive oil's OLE and HT, rich in antioxidant properties, emerge as potential treatments, promising lower toxicity and harnessing the Mediterranean Diet’s (MD)’s cancer-preventive benefits.

Further, in vivo studies and clinical trials are essential to confirm their therapeutic efficacy and safety in NB cases.

NB: A comprehensive analysis 

Overview and Genetic Insights

NB, a prevalent extracranial solid tumor in children, presents varied outcomes based on genetic alterations.

Favorable scenarios often correlate with whole chromosome changes, whereas poor prognosis are typically linked to segmental anomalies like MYCN amplification.

This gene's deregulation promotes aggressive tumor behaviors, indicating a grim prognosis through its impact on cell migration, immune evasion, and a delicate balance between proliferation and apoptosis.

The role of oxidative stress

Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) and antioxidant defenses, catalyzes cellular damage.

NB's progression and development are propelled by high ROS levels, particularly in its early stages. MYCN amplification heightens the disease's complexity by augmenting oxidative stress resistance and challenging targeted therapeutic strategies.

Antioxidant strategies in therapy

The intrinsic antioxidant system is pivotal in combating oxidative stress, suggesting a potential therapeutic avenue in NB treatment. Antioxidants such as N-acetylcysteine (NAC) and fraxetin have demonstrated efficacy in curbing NB cell proliferation by modulating ROS levels.

This underscores the necessity of integrating antioxidants into treatment plans, aiming to enhance the efficacy of conventional therapies while reducing their adverse effects.

Future research is essential to fully tap into the therapeutic potential of antioxidants in managing NB.

Exploring the Potentials of OLE and HT

OLE: A multifaceted phenolic compound

OLE is a predominant phenolic compound in olives, integral to the plant's secondary metabolism. Discovered in 1908, OLE's formation in olives decreases as the fruit matures.

This compound undergoes complex metabolic transformations in the body, creating various bioactive molecules, including HT.

OLE's biological roles are diverse, offering anti-inflammatory and neuroprotective effects by modulating several molecular pathways. In cancer, OLE has shown promise by inhibiting cell growth and promoting apoptotic pathways, making it a target of interest for its therapeutic potential.

HT: An antioxidant powerhouse

HT emerges from the enzymatic breakdown of OLE and other glycosides, known for its robust anti-inflammatory, antiatherogenic, and antithrombotic properties.

This compound has garnered attention for suppressing low-density lipoprotein (LDL) oxidation, potentially offering cancer prevention and treatment benefits. The bioavailability of HT and OLE is generally low, yet they are key components of the MD, found in olives and olive oil.

Their antioxidant mechanisms involve scavenging free radicals and chelating metals, underscoring their potential in combating oxidative stress.

The role in MD and antioxidant mechanisms

The MD, rich in OLE and HT, has been associated with numerous health benefits, including reduced cancer risk. These compounds' antioxidant action is pivotal, capable of more effectively neutralizing free radicals than vitamin E or butylated hydroxytoluene.

Interestingly, at higher doses, OLE and HT exhibit pro-oxidant activity, which may contribute to their anticancer effects by inducing oxidative stress in cancer cells.

This dual function underscores these phenolics' complex role in health and disease, highlighting the need for further research to leverage their therapeutic potential fully.

Investigating OLE and HT's potential against NB

Effects on cell lines: viability and apoptosis insights

OLE and HT exhibit potent effects against NB cells, notably affecting cell viability, proliferation, and apoptosis. OLE demonstrates dose-dependent cytotoxicity, particularly in SH-SY5Y and CHP-134 cells, while HT significantly reduces cell viability in SH-SY5Y cells, indicating strong anti-growth properties.

Both compounds trigger apoptosis, with OLE and its derivative, OLE aglycone (OLEA), disrupting key cancer cell processes such as STAT3 phosphorylation and cell migration. HT's high apoptotic rate further underscores its therapeutic potential in combating NB.

Oxidative stress reduction and challenges in in vivo utilization

The antioxidant actions of OLE and HT contribute to their therapeutic potential, with OLE binding to metal ions to prevent free radical production and HT enhancing cellular antioxidant defenses.

Despite promising in vitro results, translating these effects to in vivo contexts presents challenges due to polyphenols' poor bioavailability.

However, animal studies have indicated OLE's capacity to inhibit tumor growth and metastasis, emphasizing the need for further in vivo investigations specific to NB.

Enhancing conventional therapies and future directions

The integration of antioxidants like OLE and HT with conventional cancer treatments may offer benefits, such as increased treatment tolerance and improved patient outcomes.

While antioxidants have raised concerns about potentially diminishing the effectiveness of treatments like radiotherapy, their strategic use could reduce oxidative stress induced by chemotherapeutic agents, thus protecting normal cells and potentially reactivating dormant tumors.