Key Cancer-Fighting Compounds in Olives

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Olives have long been celebrated for their health benefits, particularly in relation to cardiovascular health, inflammation, and cancer prevention. Their potential to combat cancer stems from several bioactive compounds present in olives and olive oil that exhibit anticancer properties. Below is a detailed exploration of these cancer-fighting ingredients, their mechanisms of action, and how they work against cancer:

cancer; olives; astakos olives

Key Cancer-Fighting Compounds in Olives

  1. Oleocanthal
  2. Oleuropein
  3. Hydroxytyrosol
  4. Squalene
  5. Lignans
  6. Vitamin E
  7. Monounsaturated Fatty Acids (MUFA)
  8. Phytosterols
  9. Flavonoids and Polyphenols

1. Oleocanthal

Chemical Nature:

  • Oleocanthal is a phenolic compound responsible for the distinctive pungent taste of extra virgin olive oil.

Detailed Mechanisms:

  • Lysosomal Membrane Permeabilization (LMP):
    • Selective Cytotoxicity: Oleocanthal uniquely induces lysosomal membrane permeabilization in cancer cells but not in healthy cells.
    • Mechanism: It destabilizes lysosomal membranes, causing the release of cathepsin enzymes into the cytosol.
    • Outcome: This leads to apoptosis (programmed cell death) of cancer cells without harming normal cells.
  • Inhibition of Inflammatory Pathways:
    • COX Enzyme Inhibition: Oleocanthal inhibits cyclooxygenase (COX)-1 and COX-2 enzymes, reducing the production of pro-inflammatory prostaglandins.
    • NF-κB Pathway Suppression: It downregulates the nuclear factor-kappa B (NF-κB) pathway, decreasing the expression of genes involved in inflammation and cell proliferation.
  • Anti-Proliferative Effects:
    • Cell Cycle Arrest: Induces cell cycle arrest at the G0/G1 phase, preventing cancer cells from replicating.
    • Apoptosis Induction: Activates caspase-dependent pathways leading to apoptosis.

Signaling Pathways Affected:

  • MAPK Pathway: Modulates the mitogen-activated protein kinase (MAPK) pathway, influencing cell growth and apoptosis.
  • p53 Activation: Enhances the activity of the p53 tumor suppressor gene, promoting DNA repair and apoptosis.

2. Oleuropein

Chemical Nature:

  • Oleuropein is a secoiridoid glycoside predominant in olive leaves and fruit.

Detailed Mechanisms:

  • Antioxidant Activity:
    • Free Radical Scavenging: Neutralizes reactive oxygen species (ROS), preventing oxidative DNA damage.
    • Enzyme Modulation: Upregulates antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase.
  • Anti-Angiogenic Effects:
    • VEGF Inhibition: Suppresses vascular endothelial growth factor (VEGF), hindering new blood vessel formation essential for tumor growth.
    • MMP Regulation: Inhibits matrix metalloproteinases (MMPs), reducing tumor invasion and metastasis.
  • Induction of Autophagy and Apoptosis:
    • Autophagy Promotion: Stimulates autophagic cell death by modulating autophagy-related genes.
    • Apoptosis Triggering: Activates both intrinsic and extrinsic apoptotic pathways, increasing Bax/Bcl-2 ratio and caspase activation.

Signaling Pathways Affected:

  • PI3K/Akt/mTOR Pathway: Inhibits this pathway, leading to decreased cell growth and survival.
  • JAK/STAT Pathway: Modulates signaling involved in cell proliferation and immune response.

3. Hydroxytyrosol

Chemical Nature:

  • Hydroxytyrosol is a phenolic compound with high bioavailability and antioxidant capacity.

Detailed Mechanisms:

  • Potent Antioxidant Effects:
    • DNA Protection: Shields DNA from oxidative stress-induced mutations.
    • Lipid Peroxidation Prevention: Protects cell membranes by preventing lipid oxidation.
  • Modulation of Apoptosis:
    • Mitochondrial Pathway Activation: Disrupts mitochondrial membrane potential, leading to cytochrome c release and caspase activation.
    • Caspase Cascade Induction: Activates caspase-9 and caspase-3, key executors of apoptosis.
  • Anti-Proliferative Actions:
    • Cell Cycle Arrest: Causes arrest at the G2/M phase, halting cell division.
    • Downregulation of Cyclins: Decreases levels of cyclin-dependent kinases essential for cell cycle progression.

Signaling Pathways Affected:

  • Nrf2 Pathway Activation: Enhances expression of antioxidant response element (ARE)-driven genes.
  • Suppression of ERK1/2 Pathway: Inhibits cell proliferation signals mediated by the ERK pathway.

4. Squalene

Chemical Nature:

  • Squalene is a triterpene hydrocarbon involved in cholesterol synthesis.

Detailed Mechanisms:

  • Antioxidant Protection:
    • Lipid Soluble Antioxidant: Neutralizes lipid peroxides in cell membranes.
    • DNA Damage Prevention: Protects against oxidative DNA damage induced by free radicals.
  • Immune System Modulation:
    • Enhancement of Immune Cells: Stimulates activity of natural killer (NK) cells and macrophages.
    • Cytokine Production: Increases production of cytokines like interleukin-2 (IL-2) and interferon-gamma (IFN-γ).
  • Inhibition of Carcinogen Activation:
    • Enzyme Modulation: Reduces activity of cytochrome P450 enzymes, decreasing the activation of pro-carcinogens.

Signaling Pathways Affected:

  • Modulation of Cholesterol Pathway: Alters cholesterol biosynthesis, affecting cell membrane composition and signaling.

5. Lignans

Chemical Nature:

  • Lignans are a class of polyphenols found in plant cell walls.

Detailed Mechanisms:

  • Phytoestrogenic Activity:
    • Estrogen Receptor Binding: Acts as a weak estrogen agonist/antagonist, binding to estrogen receptors and modulating their activity.
    • Hormone Regulation: Lowers endogenous estrogen levels by inhibiting enzymes like aromatase.
  • Antioxidant Effects:
    • ROS Scavenging: Neutralizes free radicals, reducing oxidative stress.
    • DNA Protection: Prevents DNA strand breaks and mutations.
  • Anti-Proliferative Actions:
    • Cell Cycle Modulation: Induces cell cycle arrest by affecting cyclin and CDK expression.
    • Apoptosis Induction: Activates apoptotic pathways through caspase activation.

Signaling Pathways Affected:

  • Estrogen Signaling Modulation: Alters transcription of estrogen-responsive genes involved in cell growth.
  • Growth Factor Inhibition: Reduces levels of growth factors like IGF-1, which promote cancer cell proliferation.

6. Vitamin E (Tocopherols)

Chemical Nature:

  • Vitamin E is a group of fat-soluble compounds, including alpha-tocopherol, the most biologically active form.

Detailed Mechanisms:

  • Antioxidant Defense:
    • Lipid Radical Scavenger: Protects polyunsaturated fatty acids in cell membranes from peroxidation.
    • Chain-Breaking Antioxidant: Interrupts free radical chain reactions.
  • Immune Function Enhancement:
    • Cell-Mediated Immunity: Boosts T-cell function and cytokine production.
    • NK Cell Activity: Enhances the cytotoxic activity of NK cells against tumor cells.
  • Gene Expression Regulation:
    • Transcription Factor Modulation: Influences NF-κB and AP-1, reducing the expression of genes involved in inflammation and cell proliferation.

Signaling Pathways Affected:

  • Protein Kinase C Inhibition: Modulates PKC activity, affecting cell proliferation and differentiation.
  • Apoptotic Pathways Activation: Promotes apoptosis through caspase activation and modulation of Bcl-2 family proteins.

7. Monounsaturated Fatty Acids (MUFA)

Chemical Nature:

  • Oleic acid is the principal MUFA in olives and olive oil.

Detailed Mechanisms:

  • Oncogene Regulation:
    • HER2/neu Suppression: Downregulates the expression of the HER2 oncogene, overexpressed in some breast cancers.
    • Synergistic Effects: Enhances the efficacy of chemotherapeutic agents targeting HER2.
  • Anti-Inflammatory Actions:
    • Cytokine Production Reduction: Lowers levels of pro-inflammatory cytokines like IL-6 and TNF-α.
    • Eicosanoid Synthesis Modulation: Alters the production of eicosanoids, reducing inflammation.
  • Membrane Fluidity and Signal Transduction:
    • Cell Membrane Composition: Incorporation into phospholipids alters membrane fluidity, affecting receptor function and signal transduction.

Signaling Pathways Affected:

  • MAPK/ERK Pathway Inhibition: Reduces cell proliferation signals mediated by this pathway.
  • Activation of AMPK: Promotes energy balance and inhibits anabolic processes related to cell growth.

8. Phytosterols

Chemical Nature:

  • Phytosterols are structurally similar to cholesterol but are derived from plants.

Detailed Mechanisms:

  • Cholesterol Competition:
    • Absorption Reduction: Compete with cholesterol for absorption in the intestines, lowering serum cholesterol levels.
    • Membrane Effects: Alter cell membrane composition, affecting signaling pathways.
  • Apoptosis Induction:
    • Caspase Activation: Triggers apoptosis via activation of caspases-8, -9, and -3.
    • Mitochondrial Pathway: Disrupts mitochondrial membrane potential, leading to cytochrome c release.
  • Cell Cycle Arrest:
    • G1 Phase Arrest: Inhibits cyclin D1 and CDK4, halting progression through the cell cycle.

Signaling Pathways Affected:

  • NF-κB Pathway Suppression: Decreases transcription of genes involved in cell survival and proliferation.
  • Akt Pathway Inhibition: Reduces Akt phosphorylation, leading to decreased cell survival signals.

9. Flavonoids and Polyphenols

Chemical Nature:

  • Includes compounds like quercetin, luteolin, and apigenin found in olives.

Detailed Mechanisms:

  • Antioxidant Activity:
    • ROS Neutralization: Scavenges free radicals, preventing oxidative damage to DNA and proteins.
    • Metal Chelation: Binds metal ions that catalyze ROS formation.
  • Anti-Proliferative Effects:
    • Topoisomerase Inhibition: Interferes with enzymes essential for DNA replication and repair.
    • Cell Cycle Modulation: Induces arrest at various phases by affecting cyclin and CDK activity.
  • Apoptosis Promotion:
    • Mitochondrial Pathway Activation: Increases permeability of the mitochondrial membrane, leading to apoptosis.
    • Death Receptor Pathway: Upregulates death receptors like Fas, triggering extrinsic apoptotic pathways.
  • Anti-Metastatic Actions:
    • Inhibition of MMPs: Reduces activity of enzymes that degrade extracellular matrix components.
    • E-cadherin Upregulation: Enhances cell-cell adhesion, reducing metastatic potential.

Signaling Pathways Affected:

  • Wnt/β-Catenin Pathway Inhibition: Suppresses signals that promote cell proliferation and metastasis.
  • JNK Pathway Activation: Leads to increased expression of pro-apoptotic genes.

Integrative Mechanisms

Multifaceted Anticancer Actions:

  • Synergistic Effects: The combination of compounds in olives may work together to enhance anticancer effects.
  • Epigenetic Modulation: Some compounds can alter gene expression through DNA methylation and histone modification.
  • Immune System Support: Boosts overall immune function, aiding in the detection and elimination of cancer cells.

Targeting Cancer Hallmarks:

  • Sustaining Proliferative Signaling: Olive compounds disrupt signals that enable continuous cell division.
  • Evading Growth Suppressors: Reactivate tumor suppressor genes and pathways.
  • Resisting Cell Death: Overcome mechanisms cancer cells use to avoid apoptosis.
  • Inducing Angiogenesis: Inhibit new blood vessel formation necessary for tumor growth.
  • Activating Invasion and Metastasis: Reduce the ability of cancer cells to spread to other tissues.

The bioactive compounds in olives exert their anticancer effects through a complex interplay of mechanisms targeting various stages of cancer development and progression. By modulating key signaling pathways, inducing apoptosis, inhibiting proliferation, and enhancing immune responses, these compounds offer promising avenues for cancer prevention and adjunct therapy. Incorporating olives and high-quality extra virgin olive oil into the diet may contribute to these protective effects, supporting overall health and potentially reducing cancer risk.

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