A Journey Through History: From the Egyptian Pyramids to Modern Laboratories

The word "Propolis" has Greek roots: "Pro" meaning "in defense of" and "Polis" meaning "city." This naming itself is a testament to the profound understanding our ancestors had of this substance's function. The footprint of propolis use in human history is a fascinating story of wisdom and experience:

  • 📜 Ancient Egyptians: They were masters of mummification and had discovered that propolis, due to its extraordinary antimicrobial and antifungal properties, prevented the decomposition of bodies. Egyptian priests also used it as an effective medicine for treating abscesses and infections.
  • 🏛️ Greeks and Romans: The great philosopher Aristotle, in his "History of Animals," described in detail how bees use propolis to treat diseases within the hive. Hippocrates, the father of medicine, prescribed it for healing internal and external wounds, and Pliny the Elder, the Roman naturalist, wrote in his "Natural History" about its properties in reducing swelling, alleviating pain, and treating skin tumors.
  • 🇮🇷 Persian Civilization and Traditional Medicine: In traditional Persian medicine, resinous compounds with similar properties, though perhaps not by the modern name of propolis, were widely used to treat oral and dental infections, digestive problems, and to improve wound healing. In "The Canon of Medicine," Avicenna mentions the therapeutic properties of "black wax," likely a reference to raw propolis, for softening tumors and treating injuries.
  • 🎻 The Renaissance and Stradivarius Violins: In the 17th century, legendary violin makers in Italy, such as Antonio Stradivari, used propolis as a key ingredient in the varnish for their instruments. This not only gave the wood its brilliance and protection but is also believed to have played a role in the unique sound quality and unparalleled durability of these instruments.
  • ⚔️ The Battlefields: During the Boer War in South Africa and even throughout World War II, propolis was used as a natural and efficient antiseptic for dressing the wounds of soldiers on the front lines when modern medicines were scarce, saving many lives.

The Hive's Pharmacy: A Chemical Autopsy of Propolis

The power of propolis is not summarized in a single compound; rather, it is the result of an amazing "synergy" among hundreds of biologically active molecules. Like the notes of a symphony, these compounds together create an effect far more powerful than the impact of each one alone. The chemical composition of propolis is highly dependent on the plant geography (flora), season, and even the bee species. This diversity has led to the emergence of different types of propolis with unique characteristics:

  • 🟡 Poplar Propolis (European): This type, the most common in temperate regions, is mainly derived from the buds of the poplar tree. It is golden-brown in color and rich in flavonoids such as pinocembrin, chrysin, galangin, and especially CAPE. This type of propolis is renowned for its strong antibacterial and anti-inflammatory properties.
  • 🟢 Green Propolis (Brazilian): This globally renowned species is collected from a native Brazilian plant called *Baccharis dracunculifolia*. The star of this propolis is a compound named Artepillin C, which has been extensively researched, particularly in Japan, for its anti-tumor and immunomodulatory properties.
  • 🔴 Red Propolis (Brazil and Cuba): The rarest and one of the most potent types of propolis, derived from the red resin of the *Dalbergia ecastaphyllum* plant. This species is rich in isoflavonoids like vestitol and formononetin, which have shown extraordinary antioxidant and anticancer potential.
  • 🟤 Clusia Propolis (Cuba and Venezuela): This tropical type is obtained from the flowers of the Clusia plant and contains rare compounds called polyisoprenylated benzophenones (like nemorosone), which have demonstrated very high cytotoxicity against various cancer cell lines in laboratory studies.

Another crucial point is the extraction method. The active compounds of propolis must be separated from its raw mass by a suitable solvent. The most common solvent is ethanol, which can extract a wide range of flavonoids and phenolics. However, extraction with water, glycerin, or oil are other methods, each yielding a different profile of compounds. Therefore, the quality and type of propolis extract directly impact its therapeutic properties.

A Multi-Pronged Strategy: How Propolis Fights Cancer

Cancer is not a one-dimensional disease; it is a collection of complex processes that allow cells to proliferate indefinitely, escape death, create their own blood supply, and invade other parts of the body. The beauty of propolis's action is that, unlike some chemotherapy drugs that have only a single target, this natural substance simultaneously attacks multiple fronts in this war.

Halting Proliferation (Cell Cycle Arrest)

The life cycle of a cancer cell is a rapid, vicious cycle of growth and division. This cycle is controlled by proteins called cyclins and cyclin-dependent kinases (CDKs), which act like a gas pedal. Propolis compounds, especially CAPE and Artepillin C, inhibit these proteins, effectively putting their foot on the brake and stopping the cell at a checkpoint. Furthermore, propolis can reawaken tumor suppressor genes like p53 and p21 that are inactivated in cancer cells. These genes act as the cell's natural brakes, and their reactivation means a complete halt to tumor growth.

Inducing Cell Suicide (Apoptosis)

Cancer cells have learned the art of escaping death. Propolis nullifies this art. This is done through two main pathways: the intrinsic (mitochondrial) pathway, where propolis induces oxidative stress, disrupting the balance between death proteins (Bax) and life proteins (Bcl-2). This leads to the release of cytochrome C from the mitochondria and the activation of a cascade of executioner enzymes called caspases. The extrinsic (death receptor) pathway, where propolis compounds make cancer cells more sensitive to death signals sent from immune cells. They increase the number of death receptors (like TRAIL) on the cell surface, making it more prepared to receive the suicide command.

Cutting Off the Tumor's Supply Line (Anti-Angiogenesis)

For a tumor to grow beyond a microscopic size, it requires oxygen and nutrients. To achieve this, it sends signals (the most important being VEGF) to attract new blood vessels. This process is called angiogenesis. Propolis is a potent anti-angiogenic agent. Its compounds directly inhibit VEGF production by cancer cells and also prevent the growth of new blood vessel wall cells. This strategy places the tumor under an economic siege, starving it and preventing its further growth.

Blocking the Path of Invasion (Anti-Metastasis)

The most dangerous feature of cancer is its ability to metastasize, or spread to other organs. To do this, cancer cells must detach from the primary tumor, invade surrounding tissues, and enter the bloodstream or lymphatic system. This process requires enzymes called matrix metalloproteinases (MMPs), which act like molecular scissors, clearing the path for invading cells. Propolis strongly inhibits the activity of these enzymes. By affecting cell adhesion molecules, it also strengthens the connection between cancer cells, preventing their escape. This reduces the risk of metastasis and the progression of the disease to later stages.

Diagram of propolis's effect on cancerous processes

An Intelligent Partnership: Propolis Alongside Conventional Treatments

Perhaps one of the most exciting and practical aspects of research is the role of propolis as a complementary and integrative therapy. Propolis not only does not interfere with standard treatments but can also enhance their effectiveness and reduce their side effects:

  • 🎯 Increasing Sensitivity to Chemotherapy: One of the biggest challenges in treatment is the drug resistance of cancer cells. These cells activate molecular pumps (like P-glycoprotein) that eject the drug as soon as it enters. Propolis has been shown to inhibit these pumps, re-sensitizing resistant cells to chemotherapy.
  • 🛡️ Protecting Healthy Cells: Chemotherapy and radiotherapy damage healthy cells in addition to cancer cells. Due to its outstanding antioxidant properties, propolis can protect healthy cells (especially those in the liver, kidneys, and bone marrow) from this damage (a radioprotective and chemoprotective effect), while simultaneously making cancer cells more sensitive to radiation (a radiosensitizer effect).
  • 💪 Strengthening and Modulating the Immune System: Cancer grows by suppressing the immune system. Propolis is an immunomodulator. It can enhance the activity of the body's natural fighter cells, such as Natural Killer (NK) Cells and macrophages, which are on the front line of defense against tumors, while also reducing the chronic inflammation in the tumor microenvironment that aids its growth.
  • 🩹 Reducing Painful Side Effects: One of the most common side effects of treatment is mucositis (painful inflammation and sores in the mucous membranes of the mouth and digestive tract). Numerous clinical studies have shown that using propolis mouthwashes or supplements can significantly reduce the severity of this condition and improve patients' quality of life.