Mastic Kills Colon Cancer Cells
In laboratory study on human cancer cells,
it causes them to detach, degrade, and die
By Will Block
f you’ve ever laid tile, you’re probably familiar with mastic, the thick, gummy adhesive used to bond the tiles to their substrate. Different types of mastic are available for such purposes, depending on the application—mainly interior or exterior floors and walls, as well as roofs. Regardless of the formulation, the idea is to form a strong, permanent bond so the tiles won’t come loose.
I know what you’re thinking: what a boring subject, and aren’t we talking about the wrong kind of mastic here? Well, yes and no to that question, as will become apparent if you’ll be kind enough to keep reading. As for the subject matter, it’s not just the word mastic that provides the link between tiling and health concerns—it’s also the nature of tiling itself, as will also become apparent.
Real Mastic Has Medicinal Value
Let’s start by clearing up the semantic issue. The tiling mastics do not contain actual mastic, the gummy resin that exudes from mastic trees (Pistacia lentiscus), but they are its namesake. And whereas you can eat real mastic for its aromatic flavor and its time-honored (as well as newly discovered) medicinal properties, eating tiling mastic would probably land you in the hospital.
Since ancient times, mastic has been used in Mediterranean cultures as an antiseptic, a food antioxidant, a chewing gum and breath sweetener, a flavoring additive in a variety of traditional foods and drinks, and a remedy for stomachache, indigestion, and ulcers. The medicinal value of mastic lies mainly in its lethal action against a number of species of harmful bacteria, most notably Helicobacter pylori. This nasty little bug, which infects roughly half the people on earth, is the primary causative agent for nonerosive gastritis (a chronic inflammation of the stomach) and most gastric and duodenal ulcers, collectively known as peptic ulcers.*
The Best pylori Is a Dead pylori
Fortunately, most infected people do not develop ulcers, but the potential is always there, and the surest way to prevent it from being activated is to eradicate H. pylori from the GI tract. This includes the mouth, which also harbors the bug and which provides a convenient route for reinfection of the stomach and intestines (there’s no way to prevent bacteria from migrating up or down the esophagus).
Although it’s not believed to cause stomach cancer, H. pylori is strongly associated with this terrible disease: infected individuals are three to six times more likely to get stomach cancer than those who are free of infection. Thus, eradicating H. pylori from the GI tract can indirectly help prevent stomach cancer.
Looking Just Beneath the Surface
Now, on to the tiling issue. In your body, cells don’t float around freely—if they did, you’d just be a big pile of biomush. In order for distinct tissues and organs to exist as such, their constituent cells must be held together somehow. This is accomplished throughout the body by a variety of nonliving materials collectively called the extracellular matrix (ECM), which can be thought of as a kind of structural network to which the cells adhere through intermolecular forces.
Within tissues and organs, the ECM is 3-dimensional, but just beneath any surface, it’s essentially a 2-dimensional layer, to which the tightly packed surface cells are bonded, like tiles to mastic. (Aha!) These surface cells, called epithelial cells, constitute the internal and external surfaces of most tissues and organs—including the skin, glands, and blood vessels. They’re particularly tightly packed in the capillaries of the brain, where they constitute the protective blood-brain barrier. Without the underlying ECM to hold them in place, epithelial cells would just drop off and float away.
Ahoy, Cells: Remain Anchored or Die
The ECM consists mainly of a variety of complex proteins and carbohydrates (plus minerals in the case of bone matrix). Most normal cells cannot survive unless they’re anchored to the ECM—their life literally depends on it. This phenomenon is called anchorage dependence. An obvious exception to the rule is blood cells, which have to circulate freely throughout the body.
There is another exception, however, and it’s a sinister one: cancer cells, which are, by and large, not anchorage-dependent. Thus, cancer cells that have broken loose from a primary tumor can remain alive—biologists describe them as immortal—and they may be able to travel throughout the body until they find hospitable places in which to start secondary tumors. This is the dreaded process of metastasis, which is usually what kills the patient. Now let’s see what kills individual cells.
How Cells Commit Suicide
When a ceramic wall tile comes loose and falls to the ground, it will most likely break. Similarly, when an epithelial cell comes loose from its mooring and falls away, it will die (unless it’s cancerous). The death process is called apoptosis (pronounced ap-oh-TOE-sis), from the Greek for “falling away.” Apoptosis, also called “programmed cell death” or “cell suicide,” is the natural process by which many cells of the body die when they have worn out or have been damaged and need to be replaced by fresh new cells. The new cells are created when healthy cells multiply by splitting in two—a process called mitosis. (Mitosis also occurs, unchecked, in cancer cells, whose proliferation causes tumors to grow.)
This cycle of cellular life and death occurs constantly throughout the body. As old or damaged cells die, they disintegrate into membrane-bound fragments, which, when they wind up in the bloodstream, are scavenged and disposed of by phagocytes, the body’s cell-eating cells.* Apoptosis is a very general phenomenon, and it occurs under many different conditions. The particular form of apoptosis that occurs in epithelial cells as a result of detachment from the ECM (or impaired adhesion to the ECM) has a special name: anoikis (pronounced an-oh-EE-kis).
Die, Colon Cancer Cells
When epithelial cells of the colon undergo anoikis, they have a more direct route to oblivion than being eaten by phagocytes. But what if they’re cancerous and don’t die? If the cancer has invaded the underlying tissue (as cancers generally do), cancerous cells may enter the bloodstream rather than the intestinal tract; there they will probably survive and metastasize to other parts of the body. Better that they be killed before that can happen.
This brings us to a recent study of cancerous human colon cells by scientists in Florida and Greece. Their objective was to see whether mastic—the real mastic—could kill these cells in laboratory experiments. Using an extract of mastic resin from the Greek island of Chios in the Aegean Sea (where virtually all mastic comes from), the researchers incubated the cancer cells with the mastic extract at different concentrations for different lengths of time.
Mastic Gets the Job Done
They found that mastic killed the cells in a dose-dependent and time-dependent manner: the higher the mastic concentration and the longer the incubation period, the greater the killing effect. With an incubation period of 48 hours, a mastic concentration of 25 mcg/ml (micrograms per milliliter) left the cancer cells attached to the ECM; with 50 mcg/ml, the cells were about 50% detached; and with 100 mcg/ml, they were 100% detached (these numerical equivalencies were coincidental).
But wait—detachment is one thing, but dying is another, and cancer cells don’t ordinarily die when they detach from the ECM. In this case, however, they did die. Through a variety of experimental techniques, the researchers were able to deduce the following basic chain of events through which mastic killed the cancer cells by inducing anoikis:
1. Mastic interrupts the cell cycle—the process leading to mitosis—at the stage called G1, when the cell is enlarging and its organelles are multiplying. This effectively blocks the next stage of the cell cycle, called synthesis (S), in which DNA replication occurs so that both daughter cells will have a full complement of chromosomes. Both synthesis and the following stage, called G2, are necessary for mitosis to occur—but now it cannot occur.
2. Inside the cell, chemical signals are sent to numerous “anchor” proteins that are embedded in the cell wall (they project all the way through it), causing them to alter their molecular configuration in such a way that their grip on the extracellular matrix is loosened. The cell then detaches from the ECM.
Jerusalem Balsam Contained Mastic
The sticky resins, such as frankincense, myrrh, and mastic, that exude from certain types of evergreen trees have long been used as medicines called balsams (from a word of ancient Semitic origin). Balsams are fragrant because of the aromatic oils and acids they contain, and they have also been widely used as incense and perfume. Although they can be found worldwide, their recorded history begins in the Near East, where they have been used medicinally for thousands of years.
Not all balsams are of ancient origin, however. One of the most commercially successful formulations was developed in the early eighteenth century by a Franciscan monk, Antonio Menzani di Cuna, who lived in the monastery of the order of Saint Savior in Jerusalem. He was a physician and pharmacist, and in his day the Franciscan pharmacy in Jerusalem was regarded as among the finest in the Christian world (it ceased to function sometime during the mid-twentieth century).
Gold (as minute flakes in a glass shell), olibanum (frankincense, bottom), and myrrh (top). Had there been two more Magi, there might have been gifts of mastic and aloe.
Father Antonio actually developed four balsam formulations, all of which came to be known as Jerusalem Balsam (perhaps because the name appealed to Christians, Jews, and Muslims alike—a smart marketing tactic). Yet a fifth formulation called Jerusalem Balsam (as well as various other names) appeared and can still be found, in numerous variations, in several current pharmacopoeias.
The number of ingredients in the five Jerusalem Balsams ranged from four to forty, a fact that may have reflected a timeless socioeconomic reality: some people can afford only the garden-variety brand, while others can afford the premium brand. Despite the vast differences among the five formulations, they were all used as a kind of panacea, being administered both topically for all kinds of skin disorders, as well as the healing of wounds and bruises, and internally for such conditions as stomachache, worms, hemorrhoids, headaches, dizziness, ear and teeth problems, blood spitting, and even heart disease.
A multidisciplinary team of scholars from Israel recently recreated the four-ingredient formulation (from an Italian-language manuscript found in the monastery archive) so they could test it for medicinal properties. Here are the ingredients, including the botanical names as we now know them:
- Olibanum* (Boswellia species) – 6 oz
- Mastic (Pistacia lentiscus) – 4 oz
- Aloe (Aloe species, probably vera) – 3 oz
- Myrrh (Commiphora species) – 1 oz
These ingredients were macerated in 6 lb of alcohol distilled from wine, and the extract was used as a medicine for the kinds of ailments mentioned above.
The Israeli scientists duplicated the formula using specimens from the plant species most likely to have been used originally. In laboratory and animal experiments, they found that this Jerusalem Balsam exhibited significant anti-inflammatory, antibacterial, and antioxidative actions. (Curiously, they found no significant effect on wound healing, despite the balsam’s wide use for that purpose.)
Thus, modern science has confirmed the medicinal value of a remedy that was popular as a panacea throughout Europe and the Near East for about two centuries. Unfortunately, however, it’s impossible to say which ingredient is responsible for which effect. In the authors’ words,
Is the activity of the mixture due to a single chemical entity or to synergism of compounds from different plant species? Or is it an ‘entourage effect,’ … in which nonactive constituents enhance the activity of an active constituent?
We wish we knew.
- Moussaieff A, Fride E, Amar Z, Lev E, Steinberg D, Gallily R, Mechoulam R. The Jerusalem balsam: from the Franciscan monastery in the old city of Jerusalem to Martindale 33. J Ethnopharmacol 2005; online preprint.
3. The process of apoptosis begins. It’s complex, but its central feature is the activation of a family of death proteins called caspases, which systematically degrade structural proteins in the cell’s cytoplasm, and chromosomal DNA in the cell’s nucleus. This kills the cell, which breaks apart into fragments that are disposed of in one way or another.
Which Components of Mastic Are Responsible?
Apoptosis in general is caused by the action of caspases, but something has to activate them, and in this case, that something appears to be one or more chemical compounds in the mastic extract. What these compounds are, however, remains unknown, because only a few of mastic’s constituents have yet been isolated and identified.
Thus, the biochemical mechanism of mastic’s action is unclear. Using the technique of electron microscopy, however, the researchers obtained visual evidence of mastic’s gradual destruction of the cancer cells. Over a 72-hour period, the initially robust-looking cells were seen to deteriorate and ultimately disintegrate into lifeless fragments.
Mastic vs. Mastic
For people who take mastic to alleviate gastrointestinal problems caused by H. pylori, it’s too soon to say whether this discovery might have practical benefits farther down the pipeline. There is, after all, a world of difference between cell cultures in a petri dish and the inside of a colon. Nonetheless, it’s gratifying to learn that the scope of mastic’s potential health benefits has been enlarged in this way. And there’s a strange irony in the fact that mastic from a tree can kill cancer cells by eroding their ability to be held in place by the extracellular matrix, the body’s own “mastic.”
- Al-Said MS, Ageel AM, Parmar NS, Tariq M. Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity. J Ethnopharmacol 1986;15:271-8.
- Huwez FU, Thirlwell D, Cockayne A, Ala’Aldeen DAA. Mastic gum kills Helicobacter pylori. N Engl J Med 1998;339(26):1946.
- The Merck Manual of Diagnosis and Therapy, 17th ed. Merck Research Laboratories, Whitehouse Station, NJ, 1999, pp 245-56.
- Balan KV, Demetzos C, Prince J, Dimas K, Cladaras M, Han Z, Wyche JH, Pantazis P. Induction of apoptosis in human colon cancer HCT116 cells treated with an extract of the plant product Chios mastic gum. In vivo 2005;19:93-102.
Will Block is the publisher and editorial director of Life Enhancement magazine.