In addition to its antioxidant, anti-bacterial, and anti-ulcer properties …

Mastic Helps
Prevent Oral Cancer

… and operates as a potent antitumor agent
that inhibits growth and induces cell suicide
By Will Block

The reason I will not exhibit this picture is that I am afraid
that I have shown in it the secret of my own soul.

— Oscar Wilde, The Picture of Dorian Gray

O

ral cavity carcinoma or oral tongue carcinoma is no laughing matter, as Dorian Gray might confide. In part, that’s because these distinct forms of cancer—arising from the squamous cells, the thin, flat cells that line the oral cavity—can manifest in the mouth, on the tongue, the lips, or the skin of the face. According to a recent study,1 the incidence of oral tongue squamous cell carcinoma has been rising in young white American men and women. From 1975 to 2007 (when the study ended), the incidence has been increasing in young white men and white women 18 to 44 years of age, but the trend is most pronounced in white women.

In the study, published in the Journal of Clinical Oncology, researchers reported that the incidence of oral cavity squamous cell carcinoma was declining for all age groups. And the incidence of oral cavity and tongue cancer also was decreasing overall for nonwhite individuals.

However, in the overall age group (18 to 44 years of age), the incidence of oral tongue cancer climbed 28% during the three decades of the study. And among white people in this age group, the incidence increased 67%. Most dramatic was the rise for white women in this age group, which jumped by 111%.

Historically, cancer of the oral cavity has been associated with older men with histories of significant tobacco and alcohol use. Yet during the past 30 years, the incidence of oral cavity squamous cell carcinoma has been falling, while the incidence of oropharyngeal (oral airway) squamous cell cancer has been increasing, according to the study. These trends might be explained by the decreased use of tobacco and the association between the carcinogenic strains of human papillomavirus (HPV) and oral cavity cancer. But this is not clear.

HPV Not Associated

Unlike cancers of the tonsil and base tongue areas within the oropharynx, oral cavity and oral tongue squamous cell carcinomas are rarely associated with HPV infection. Moreover, the demographics of HPV-related head and neck malignancies are distinctly different from those associated with HPV. HPV-associated head and neck cancers are far more likely to be white men who do not smoke. On the other hand, at the University of North Carolina Hospital in Chapel Hill, where the young patients with head and neck squamous cell carcinomas were examined, most were young white women, who were nonsmokers and nondrinkers.

“Our findings suggest that the epidemiology of this cancer in young white females may be unique and that the causative factors may be things other than tobacco and alcohol abuse,” said Dr. Bhishanjit Chera, lead author of the study.2 “Based on our observations and the published data, it appears that these cases may not be associated with the human papillomavirus. We are actively researching other causes of this cancer in this patient population.”

It is possible that they are being caused by a different virus or another subtype of HPV, Dr. Chera told Medscape Medical News. “There are over 100 subtypes but only a handful are associated with malignancy, and we only test for the high-risk types.”

Possible Emerging Clinical Entity

The lack of association between HPV and oral tongue squamous cell carcinoma in young white women “may be an emerging and distinct clinical entity, although future research is necessary before broad conclusions can be drawn, note the study’s authors.” The medical mystery is yet unsolved.

Dentists and primary care physicians should be more aware that oral tongue squamous cell carcinoma are particularly rife in young white women. It is typically in the dentist’s office that most people are examined for this condition. “Dentists should not only examine dental health but also examine the tongue. They are in a position to provide effective screening,” advocated Dr. Chera.

Conventional Treatment

Illusion is the first of all pleasures. — Oscar Wilde
If oral squamous cell carcinoma lesions are found, surgery is considered the primary treatment modality, which is more effective in the early stage. While a combination of surgery and radiotherapy is necessitated in more advanced lesions, radiation-only therapy shows a poor survival rate (less than 25%) in inoperable lesions. Egad! The concurrency of chemo-radiotherapy has recently emerged as a new treatment modality, but it is limited to specific agents, high cost, and results in more serious side effects, such as healing disorder, oral mucositis, and nausea with vomiting. These make it difficult to apply clinically. But why go there if preventive medicine, (i.e., supplementation) can help to avoid this route.

Mastic Inhibits Oral Squamous Carcinoma

In a new study, Chios mastic gum (CMG) extract was investigated as a potential anti-tumor agent for oral squamous cell carcinoma in vitro at Yanbian University Hospital, Yanji City, P.R. China.3 The researchers examined the effects of CMG extract on the growth of an oral squamous cell carcinoma cell line. And to determine whether CMG could induce apoptosis through the activation of caspase-3—a member of the cysteine-aspartic acid protease (caspase) family known to be the key mediator of apoptosis (cell suicide)—using the common chemotherapeutic agent paclitaxel (trademarked as Taxol®) as a control.

The Executioner Enzyme

What they found, using an assay for measuring the activity of the caspase enzyme, suggested that both CMG and paclitaxel inhibited the proliferation of a human oral squamous carcinoma cell line in a time and dose dependent manner. Furthermore, 10µg/mL of CMG and 50µg/mL of paclitaxel caused genomic DNA fragmentation at 24 hour and the same amounts of each agent caused cleavage of procaspase-3 in western blot analysis, designed to detect specific proteins. Procaspase-3, when activated, changes into the executioner enzyme caspase-3 and initiates programmed cell death, called apoptosis. These results indicate CMG’s potential as a superb anti-tumor agent.

Mastic: Anti-Ulcer; Anti-Carcinogenic for Colon and Prostate

CMG is a white resin obtained from the trunks and leaves of Pistacia lentiscus var. Chia, the most potent of which is grown and harvested on the Greek Island of Chios. Already known to have anti-Helicobacter pylori and thus anti-ulcer properties (see “Discovering Antibacterial Mastic” in the April, 1999 issue, “Mastic Creates Gastrointestinal Harmony” in the April, 2002 issue, and “Mastic Soothes Bellyaches” in the February, 2010 issue, among a total of 108 articles in Life Enhancement’s online library) CMG also has been found to induce apoptosis of human colon cancer cells (see “Mastic Kills Colon Cancer Cells” in the September, 2005 issue) and inhibits growth of prostate cancer cells (see “Mastic May Help Against Prostate Cancer” in the July, 2006 issue).

Mastic Fights Crohn’s Disease

It has also been reported that Crohn’s disease patients with mild to moderate activity subjected to mastic treatment seemed to improve clinically and to have better-regulated inflammation and antioxidant status (see “Mastic Reduces Inflammation in Crohn’s Disease” in the February, 2008 issue). Crohn’s disease is a form of inflammatory bowel disease. The lead study in the aforementioned article concluded that the use of natural products, such as mastic, as a primary treatment in Crohn’s disease merited wider support and research, especially given the harm of long-term corticosteroid use. Another study has readdressed the use of mastic in treating Crohn’s disease,4 finding that mastic could possibly have a therapeutic role in Crohn’s disease, by regulating oxidant/antioxidant balance and modulating inflammation.


Mastic at lower concentration showed
greater potential effects than
paclitaxel, against oral carcinoma.


Mastic as Natural Chemotherapeutic Agent

In a recent study, CMG extract has also been reported to operate as a natural chemotherapeutic agent, able to induce growth inhibitory and apoptotic effects.5 This study found that CMG induces an anoikis (from a Greek word meaning “homelessness,” or anchorage-dependent) programmed cell death in a colon cancer cell line that includes events associated with caspase-dependent pathways and thus serve as a chemotherapeutic agent for the treatment of human colon and other cancers.

Since its approval by the FDA for the treatment of advanced ovarian cancer in 1992, paclitaxel has been demonstrated as one of the most active anticancer drug agents for the therapy of ovarian, breast, non-small cell lung cancer, AIDS-related Kaposi’s sarcoma, bladder, prostate, esophageal, head and neck, and cervical and endometrial cancers.6

Better than Taxol without the Side Effects

In the current Chinese study, the design was intended to examine the effects of the CMG extract on the growth of a oral squamous cell carcinoma cell line and to determine whether CMG could induce apoptosis through the activation of caspase-3, which is known to be the key mediator of apoptosis. Commonly used chemotherapeutic agent paclitaxel was used as the control.

In the caspase assay, both agents showed growth inhibitory effects time- and dose-dependently, with CMG extract showing greater potential effect than paclitaxel at low concentration (5~10 ìg/mL). In the DNA fragmentation analysis, the growth inhibitory effect of CMG extract occurs through apoptosis. Another type of measure, western blot analysis, showed that the apoptosis was caspase-3 dependent. Apoptosis—of whatever sort by either programmed or physiological cell death—plays an important role in certain pathologic events.

Also, as a result of DNA electrophoresis, 10 µg/mL of CMG extract and 50 µg/mL of paclitaxel caused characteristic DNA fragmentation of the genomic DNA at 24 hours and 10 µg/mL of CMG extract and 50 µg/mL of paclitaxel caused fragmentation of the genomic DNA as early as 24 hours. These results show that both agents induce a growth inhibitory effect through apoptosis and that CMG extract may have greater potency than paclitaxel.

The activation caspases plays a key role in the initiation and execution of apoptosis induced by various stimuli and among the several different members of caspases identified in mammalian cells. In fact, caspase-3 plays a direct role in the proteolytic cleavage of the cellular proteins responsible for progression to apoptosis, as we have already stated. In the currect study, CMG extract and paclitaxel caused the dose and time-dependent proteolytic cleavage of procaspase-3. Although the detailed mechanism of the induction of apoptosis by CMG extract has not been determined, it has been hypothesized that CMG extract induce apoptosis through the activation of caspase-3.

Prevention Rather Than Surgery or Chemo-Radiotherapy

In conclusion, CMG extract and paclitaxel inhibited growth and induced apoptosis of a line of oral cancer cells in vitro and CMG extract had greater antitumor potency than paclitaxel. Although the results reported here are limited to in vitro findings, they may serve to direct new studies that will expand the use CMG for natural chemotherapy alongside other anticancer agents. One last point, because mastic has such low toxicity, and the alternatives to prevention are so vile, an ounce of prevention may be worth a ton of surgery or chemo-radiotherapy, or both.

References

  1. Patel SC, Carpenter WR, Tyree S, Couch ME, Weissler M, Hackman T, Hayes DN, Shores C, Chera BS. Increasing incidence of oral tongue squamous cell carcinoma in young white women, age 18 to 44 years. J Clin Oncol 2011 Apr 10;29(11):1488-94.
  2. Nelson R. Oral tongue cancer rates rising in young white women. Medscape Medical News: Oncology. http://www.medscape.com/viewarticle/739419. Updated March 22, 2011. Accessed January 22, 2012.
  3. Li S, Cha IH, Nam W. Chios mastic gum extracts as a potent antitumor agent that inhibits growth and induces apoptosis of oral cancer cells. Asian Pac J Cancer Prev 2011;12(7):1877-80.
  4. Gioxari A, Kaliora AC, Papalois A, Agrogiannis G, Triantafillidis JK, Andrikopoulos NK. Pistacia lentiscus resin regulates intestinal damage and inflammation in trinitrobenzene sulfonic acid-induced colitis. J Med Food 2011 Nov;14(11):1403-11.
  5. Balan KV, Prince J, Han Z, Dimas K, Cladaras M, Wyche JH, Sitaras NM, Pantazis P. Antiproliferative activity and induction of apoptosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia. Phytomedicine 2007 Apr;14(4):263-72.
  6. Fu Y, Li S, Zu Y, Yang G, Yang Z, Luo M, Jiang S, Wink M, Efferth T. Medicinal chemistry of paclitaxel and its analogues. Curr Med Chem 2009;16(30):3966-85.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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