Transforming growth factor beta (TGF-B) signaling pathway is involved in many different cell functions. It is also related to many different diseases including cancer, Alzheimer's, heart diseases, and connective tissue diseases like Marfan and Loey-Dietz Syndrome. In cancer, TGF-B causes metastasis, or the spread of cancer.
C. elegans are microscopic roundworms, and the type being studied are transgenic. In the worms, a gene along the TGF-B signaling pathway, DBL-1, has been over-expressed, resulting in worms longer than wild type worms. If a chemical can inhibit the TGF-B pathway it can be seen in the length of the worms. Lastly, C. elegans have never been studied in this way, most studies look at genes along the pathway, not testing if chemicals can inhibit the pathway.
Both sanguinarine and berberine are plant based alkaloids, which is a group that also includes morphine, nicotine, and caffeine. Berberine is known to have anticancer effects and inhibit the TGF-B signaling pathway, so if the worms treated with berberine are shorter than the control groups, it will prove these worms are a good model for TGF-B activity. Sanguinarine, however, is less studied, and many of the existing studies give conflicting conclusions, but because it has a similar chemical structure to berberine I predicted they would have a similar, anti cancerous, effect.
to the chemical, the age had to be synchronized to control for differences in length based on age. This is done through a procedure that kills the adult worms on a plate, while leaving the more durable eggs still alive. The worms are then transferred to plates with the chemicals on them. There are high and low concentrations of both sanguinarine and berberine plates, as well as control plates with ethanol or nothing on them. The worms sit on these plates for 24 hours before being photographed. Those photos are then analyzed using photo processing software to find the length of the worms.
A total of 7 trials were run, and 5,357 worms were photographed. The conclusions drawn from the results was that berberine inhibits the TGF-B signaling pathway, shown in shorter worms compared to other conditions. Berberine is known to inhibit the TGF-B signaling pathway, and because the results support this, these results also support the conclusion that the transgenic worms are a good model for TGF-B signaling activity. The sanguinarine treated worms were longer than the control, so sanguinarine increased TGF-B signaling.
Although sanguinarine should not be further researched as a cancer drug because it would likely increase metastasis, it should be further researched as a drug to treat arterial heart diseases because it increases TGF-B signaling. Berberine's ability to inhibit the pathway should be researched as a drug to treat not only cancer, but also Alzheimer's, Marfan syndrome, and Loey-Dietz syndrome. Future studies should use model organisms more directly related to the targeted diseases to confirm these findings.