The anti-tumor activity of hydroxytyrosol

Hydroxytyrosol (HT), a natural phenolic compound primarily found in olive leaves and olive oil, has attracted widespread attention due to its diverse biological activities such as antioxidant and anti-inflammatory effects. In recent years, research on its anti-tumor potential has gradually extended from in vitro cell experiments to animal models, providing important basis for its clinical application.

I. Exploration of Anti-tumor Mechanisms in Cell Experiments

In vitro cell experiments have shown that hydroxytyrosol exhibits significant inhibitory effects on various tumor cells (such as breast cancer, colon cancer, lung cancer, liver cancer, etc.), with its core mechanisms summarized as follows:

Inducing tumor cell apoptosis: Hydroxytyrosol can activate the mitochondrial apoptotic pathway (e.g., upregulating Bax protein and downregulating Bcl-2 protein), promoting the release of cytochrome c from tumor cells, and ultimately initiating the cascade reaction of caspases family proteases, leading to cell apoptosis. For example, in experiments with human breast cancer MCF-7 cells, the proportion of apoptotic cells reaches 3-5 times that of the control group 24 hours after hydroxytyrosol treatment, showing a dose-dependent manner.

Inhibiting cell proliferation and causing cycle arrest: Studies have found that hydroxytyrosol can arrest tumor cells in the G1 or S phase, reducing DNA replication and cell division. Its mechanism is related to the downregulation of cell cycle regulatory proteins such as cyclin D1 and CDK4, especially in colon cancer HT-29 cells, which can significantly reduce the cell proliferation index.

Inhibiting tumor angiogenesis: The growth and metastasis of tumors depend on new blood vessels to provide nutrients. Hydroxytyrosol blocks the migration and tubular structure formation of vascular endothelial cells by inhibiting the expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), thereby inhibiting tumor angiogenesis. In the lung cancer A549 cell model, its inhibition rate on VEGF can reach 40%-60%.

Synergistic effects of antioxidant and anti-inflammatory activities: The strong antioxidant property of hydroxytyrosol can scavenge reactive oxygen species (ROS) in the tumor microenvironment, reducing DNA oxidative damage; at the same time, it can inhibit inflammatory pathways such as NF-κB, reduce the secretion of tumor-related inflammatory factors (e.g., TNF-α, IL-6), and disrupt the survival microenvironment of tumor cells.

In addition, hydroxytyrosol has been found to enhance the sensitivity of tumor cells to chemotherapeutic drugs (such as cisplatin and doxorubicin). By downregulating the expression of multidrug resistance genes (e.g., MDR1), it reverses the drug resistance of tumor cells, which provides new ideas for combined medication.

II. Verification of Anti-tumor Activity in Animal Models

The positive results of in vitro experiments have promoted research on hydroxytyrosol in animal models, and its anti-tumor effects have been confirmed in various tumor-bearing animal models:

Solid tumor models: In nude mouse xenograft models (e.g., human breast cancer MDA-MB-231 xenografts), intraperitoneal injection or gavage of hydroxytyrosol (50-200 mg/kg) can significantly inhibit tumor volume growth, with a tumor inhibition rate of 30%-50%. Moreover, the number of apoptotic cells in tumor tissues increases significantly, and vascular density decreases. In the mouse liver cancer H22 xenograft model, hydroxytyrosol can also reduce the level of alpha-fetoprotein (AFP) in serum, indicating its inhibitory effect on tumor progression.

Metastasis models: Tumor metastasis is a key factor leading to treatment failure, and hydroxytyrosol has shown anti-metastatic potential in animal models. For example, in the mouse melanoma B16 lung metastasis model, oral administration of hydroxytyrosol can reduce the number of lung metastatic foci, and its mechanism is related to inhibiting the activity of matrix metalloproteinases (MMP-2, MMP-9), which play a key role in tumor cell invasion and metastasis.

Safety and synergistic therapy: Animal experiments have shown that hydroxytyrosol has low toxicity. At effective tumor-inhibiting doses, it has no significant impact on mouse weight, liver and kidney functions, which is better than some chemotherapeutic drugs. More importantly, it can enhance the therapeutic effect when used in combination with radiotherapy or chemotherapy: in the mouse colon cancer CT26 model, the combination of hydroxytyrosol and 5-fluorouracil increases the tumor inhibition rate by 20%-30% compared with single drug use, and can reduce chemotherapy-induced intestinal damage and weight loss.

III. Challenges and Prospects from Experiments to Clinical Practice

Although cell and animal experiments have confirmed the anti-tumor activity of hydroxytyrosol, its clinical transformation still faces challenges: first, hydroxytyrosol has a fast metabolism and low bioavailability in the body, and formulation technologies (such as nano-encapsulation, liposome encapsulation) are needed to extend its action time; second, its anti-tumor effect is tumor type-specific, and the administration plan needs to be optimized for different cancer types; third, there are differences between animal models and the human tumor microenvironment, and further clinical trials are needed to verify its safety and effectiveness.

In recent years, research on prodrug design and combined medication strategies based on hydroxytyrosol has gradually been carried out, laying a foundation for its application in tumor prevention and adjuvant therapy. Future research should focus on clarifying its mechanism of action in the human body and optimizing the administration route, promoting this natural compound from the laboratory to the clinic, and providing a new natural candidate drug for tumor treatment.