6-shogaol is a bioactive compound of ginger.

For decades, it has been shown to have various biological effects on the human body, such as analgesia and reducing fevers. 6shogaol is particularly potent towards two breast cancer cell lines. In fact, the IC50 value for 6-shogaol is the lowest for these two cell lines, which means that it is more effective than even gingerol in its antitumour properties. This is piques interest as gingerol is already being used in cancer treatment. In the cell line MDA MB 231, it is the only compound shown to even have an antitumour effect. However, the mechanism of action is still unknown. Data of the NCI-60, which is a set of human cancer cell lines derived from many tissues is shown. These results showed that 6-shogaol had the most dramatic effect on the two cell lines highlighted. Using the data, we performed a COMPARE analysis which is an algorithm that compared the pattern of cell line sensitivity of 6-shogaol to many other compounds. In theory, if the pattern of 6-shogaol is the same as that of another compound, one can suspect that the two share the same mechanism of action. Unfortunately, none of the compounds shared a similar pattern. Therefore, 6-shogaol has a unique mechanism of action that has not been reported yet. A previously performed microarray analysis shows several genes related to its anticancer properties have been discovered to be downregulated and upregulated. When an online algorithm called the connectivity map was performed, the natural ligand 15-delta prostaglandin J2 was found to have one of the highest maximum connectivity and has the second highest ranking. Furthermore, comparing the chemical structures of 15=delta prostaglandin and 6-shogaol, we can see that they have very similar structures. As 15-delta prostaglandin is a PPAR agonist, this led us to think that 6-shogaol may be a PPAR agonist.

PPAR functions as a ligand-dependent transcription factor and is a nuclear hormone receptor. When it binds to another receptor called Retinoid X Receptor (RXR), this new complex then binds to specific DNA sites called Peroxisome Proliferator Response Elements (PPREs) which then regulate the expression of genes. PPAR has natural ligands such as 15-delta prostaglandin J2, and synthetic ligands have also been produced. This includes the thiazolidinediones which is a class of anti-diabetic drugs. This means that PPAR agonists have traditionally been used to treat diabetes. On further literature review, several studies have shown that PPAR agonists induces terminal differentiation in liposarcomas and stabilises prostate cancer. The more differentiated a cancer cell, the better the prognosis of the cancer, and the less malignant. In breast and colon cancer, which we will be researching, PPAR agonists lowers cellular proliferation. And thiazolidinediones actually induces mRNA which codes for PPAR in these cells. In colon cancer, mutations involving the loss of function of PPAR have been strongly associated with malignancy.