Informace o publikaci
Docosahexaenoic acid sensitizes colon cancer cells to apoptotic effect of TRAIL by modulation of lipid and apoptotic signalling pathways
| Autoři | |
|---|---|
| Rok publikování | 2011 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Recently, it is suggested that some dietary polyunsaturated fatty acids (PUFAs) play an important role in suppression of colon cancer. Namely n-3 PUFAs, such as docosahexaenoic acid (DHA), showed antiproliferative and apoptotic effects in colon cancer cells. However, DHA is preferentially considered as supporting agent in combined anticancer therapy. TNF-related Apoptosis Inducing Ligand (TRAIL) is cytokine able to induce apoptosis in cancer cells with little effect on normal cells. It is promising for cancer treatment, but some cancer cells appeared to be resistant to TRAIL-induced apoptosis. We showed that pretreatment with physiological doses of DHA results in significantly enhanced TRAIL-induced apoptosis of otherwise resistant human colon cells as documented by increased caspase activation and cleavage of their substrates. We demonstrated activation of crucial mitochondrial proapototic molecules, such as Bax and Bak. Cellular lipid analysis (HPLC-MS-MS) revealed that DHA in combination with TRAIL increased amount of specific classes of ceramides, which are suggested to influence cancer cell resistance to TRAIL. In summary, our results showed the ability of DHA to enhance TRAIL-induced apoptosis in resistant colon cancer cells and suggest the role of specific lipid classes in these effects. |