Research into terpenoids including their effect on cancers was initiated by scientists at
Terpenoids are a class of hydrocarbons that are the principal component of gums, balsams, and various 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 or cold, damage, etc. Many compounds of this class could potentially have
At present, genuinely new drugs are notoriously costly to develop. However, it is much easier to register a drug based on a compound that was synthesized in the past and has since been proved to have new properties. The development of such drugs requires far less investment. Trademarked as Abisil, the drug based on Siberian fir terpenoids is already used externally for its medical benefits including
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. As every 2 or 3 days the cells in a culture form a continuous layer of sufficiently high density, they 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 (gene expression levels) were used as cell aging markers. These variations in gene activity were compared between cells from different
Exposure of cells to the test compound caused an increase in the expression of the two genes GADD45B and GADD45A by factors of 2 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 3. 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 senescent cells 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 6th and 3rd deadliest varieties of the disease respectively. The researchers have tested the effect of Siberian fir terpenoids on human cell lines of colon adenocarcinoma (
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 (
Other genes whose overexpression was observed by the scientists upon exposure of cancer cells to the test compound include
The study has thus demonstrated the potential