Mastic Kills Colon Cancer Cells


Since ancient times, mastic (Pistacia lentiscus) 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
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.

Looking Just Beneath the Surface
In your body, cells don’t float around freely- 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.
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.

Do Cells Commit Suicide?
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 , from the Greek for “falling away.” Apoptosis, also called “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. 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.

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. it will be much better if they will 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, 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 ( the scientists from Florida and Greece) 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 one second- 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, 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.
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 for this?
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.

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 line. 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".
References
1.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.

2.Huwez FU, Thirlwell D, Cockayne A, Ala’Aldeen DAA. Mastic gum kills Helicobacter pylori. N Engl J Med 1998;339(26):1946.

3.The Merck Manual of Diagnosis and Therapy, 17th ed. Merck Research Laboratories, Whitehouse Station, NJ, 1999, pp 245-56.

4.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.