Fir extract could have anti-cancer and anti-aging properties

February 28, 2017, Moscow Institute of Physics and Technology
Slider. Credit: MIPT

Scientists from the Engelhardt Institute of Molecular Biology and MIPT have studied the effects of Siberian fir terpenoids on senescent and human cancer cell lines at the genetic level. Research into terpenoids, including their effect on cancers, was initiated by scientists at Initium-Pharm Ltd. The study was published in the biomedical journal Oncotarget, and the results have attracted the interest of geneticists.

Terpenoids are a class of hydrocarbons that are the principal component of gums, balsams, and essential oils. Large volumes of terpenoids are produced by conifers for protection against diseases and invading insects, and in response to unfavorable environmental factors such as exposure to excessive heat, cold or damage. Many compounds of this class could potentially have anti-aging and anti-cancer properties. For example, extracts from the Damask rose, which is rich in a terpenoid called citronellol, have been shown to increase the lifespans of fruit flies by protecting them against iron toxicity and enhancing their resistance to oxidative stress. Betulinic acid, a lupane-type triterpene derived from birch trees, has demonstrated anti-bacterial, antimalarial, and anti-inflammatory properties, as well as cytotoxicity toward cancer . Moreover, both the anti-aging and anti-cancer properties have been observed for such terpenoids as ursolic (in apples), maslinic and oleanolic acids (extracted from olive oil).

At present, genuinely new drugs are costly to develop. However, it is much easier to register a drug based on a compound synthesized in the past that has since demonstrated previously unknown properties. The development of such drugs requires far less investment. Trademarked as Abisil, the drug based on Siberian fir terpenoids is now used externally for its anti-inflammatory, wound-healing, and anti-bacterial medicinal properties. The researchers set out to study its anti-aging and anti-cancer properties in greater detail.

Impact on senescent cells

To study the effect of Siberian fir terpenoids on cellular senescence, the scientists used a technique called cell passaging. Passaging, or subculturing, refers to the process of transferring an existing cell culture to a fresh growth medium. The cells used in the experiment were human connective tissue cells known as fibroblasts. Every two or three days, the cells in a culture form a continuous layer of sufficiently high density, and need to be detached from their growth surface and transferred to a fresh culture medium. Passaging is necessary due to the accumulation of toxic products of cell metabolism and the depletion of nutrients. The number of passages a culture has experienced is a useful characteristic, because it gives an idea of how many divisions the cells in this culture have undergone, and therefore how much they have aged.

The scientists thus used cell passaging to model aging. Variations in the amount of all kinds of RNA produced by a cell () were used as cell aging markers. These variations in gene activity were compared between cells from different passages—both untreated and exposed to the substance. Having set a twofold change in levels as the threshold of significance, the researchers obtained the following data: While 43 genes in the fibroblasts from the 13th passage exhibited increased expression (i.e., more RNA was produced by the cells) and the expression of 67 genes was decreased, the number of genes with significantly increased/decreased expression in fibroblasts from the sixth passage was 21 and 16, respectively. This means that as a cell ages, the effect of Siberian fir terpenoids on gene expression becomes more pronounced.

Exposure of cells to the test compound caused an increase in the expression of the two genes GADD45B and GADD45A by factors of two and 1.5 respectively. Both of them belong to a gene family whose members have been linked to tumor suppression and longevity.

Treatment with Siberian fir terpenoids coincided with an increase in the expression of heat shock genes (the cell's mechanism of response to elevated temperatures) by a factor of 1.5 to three. These genes play a major role in the assembly, folding and transport of complex proteins, as well as in degrading and recycling unneeded proteins. By analyzing cell pathways induced by Abisil treatment and other cellular mechanisms involved in the experiment, the scientists concluded that the drug is capable of restoring gene expression in to the level of younger cells.

Some of the genes showed increased expression

According to a statistics report citing global mortality rates for various types of cancer, pancreatic and colon cancer are the sixth and third deadliest varieties of the disease respectively. The researchers have tested the effect of Siberian fir terpenoids on human of colon adenocarcinoma (Caco-2) and pancreatic adenocarcinoma (AsPC-1).

The experiment revealed an increased level of expression of the three genes of the GADD45 family, viz., GADD45A, GADD45B, and GADD45G, both in normal fibroblasts and in tumor cell lines (AsPC-1 and Сасо-2). Mutations in the GADD45 genes are often accompanied by the initiation and progression of malignancies. In addition, these genes are known to mediate the effects of several chemotherapeutic drugs.

Other whose overexpression was observed by the scientists upon exposure of to the test compound include DUSP1–2, DUSP4–6, and DUSP8. Genes of the DUSP family are responsible for the suppression of the MAPK signal transduction cascade, which means they act as tumor suppressors and chemotherapy mediators.

The study has thus demonstrated the potential anti-aging and anti-cancer effects of Siberian fir terpenoids, opening up possibilities for their wider application in the future.

Explore further: Genes that control cellular senescence identified

More information: Oncotarget, 10.18632/oncotarget.13467

Related Stories

Genes that control cellular senescence identified

September 13, 2016
A research group including Professor KAMADA Shinji, Research Fellow NAGANO Taiki (both from the Kobe University Biosignal Research Center), and Unit Chief ENARI Masato (National Cancer Research Institute) has succeeded in ...

Evidence supports therapeutic potential of plant-based terpenoids for skin diseases

June 15, 2015
A review of clinical studies that used terpenoids to treat a variety of dermatological diseases demonstrated that this diverse class of phytochemicals may benefit patients with actinic keratosis, cutaneous candidiasis, hyperpigmentation, ...

Study identifies enzyme key to link between age-related inflammation and cancer

February 3, 2016
For the first time, researchers have shown that an enzyme key to regulating gene expression—and also an oncogene when mutated—is critical for the expression of numerous inflammatory compounds that have been implicated ...

Researchers prove antitumoral potential of a compound derived from olives

March 10, 2016
Researchers from the universities of Granada, Barcelona and Jaen prove that maslinic acid, a natural triterpene found in high concentrations in the waxy skin of olives is effective in Caco-2 p53-deficient colon adenocarcinoma ...

Anti-tumor immunity identified with new ovarian cancer treatment strategy

September 13, 2016
Few effective treatments have been approved to treat ovarian cancer, the deadliest of all cancers affecting the female reproductive system. Now, new research from The Wistar Institute demonstrates how a drug already in clinical ...

Researchers identify way radiation may fight cancer cells escaping immune system

February 2, 2016
A team of Georgia State University researchers is fighting cancers using a combination of therapies and recently found ways that radiation could maximize responses to novel immune-based therapeutic approaches to fight cancer.

Recommended for you

Week 34 of pregnancy reduces breast cancer risk: study

October 23, 2018
Women's bodies undergo a "striking" change during a specific week of pregnancy that can significantly reduce their risk of developing breast cancer later in life, scientists said Tuesday.

New combination treatment flips the switch on melanoma cells

October 23, 2018
Think of the protein BH3 like a finger that turns off a cancer cell survival switch. The problem is that most cancer cells have found ways to remove this "finger—commonly, by breaking the action of a gene called p53 that ...

New kind of compound shows early promise against prostate cancer

October 23, 2018
A new type of molecule blocks the action of genes that drive the growth of therapy-resistant prostate cancer, a new study finds.

Desperate & duped? GoFundMe means big bucks for dubious care

October 23, 2018
People seeking dubious, potentially harmful treatment for cancer and other ailments raised nearly $7 million over two years from crowdfunding sites, a study found.

Marker found for condition that causes numerous tumors

October 23, 2018
UT Southwestern researchers have made a major advance in uncovering the biology of how thousands of disfiguring skin tumors occur in patients troubled by a genetic disorder called neurofibromatosis type 1 (NF1). This scientific ...

Urban and rural rates of childhood cancer survival the same, study finds

October 23, 2018
Childhood and adolescent cancer survival in the United States does not vary by rural/urban residence at the time of diagnosis, finds a new study from the Brown School at Washington University in St. Louis.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.