Naslov
The Effect of Raloxifene Hydrochloride on NAD+/NADH Level in Cancer Cells

Autori
Oklopčić, Rebeka Monika

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, diplomski rad, diplomski

Fakultet
UNIVERSITE GRENOBLE ALPES

Mjesto
GRENOBLE ALPES

Datum
07.07

Godina
2022

Stranica
14

Mentor
Novak Kujundžić, Renata

Ključne riječi
nicotinamide adenine dinucleotide ; nicotinamide N-methyltransferase ; aldehyde oxidase ; raloxifene hydrochloride ; dimethyl sulphoxide

Sažetak
Nicotinamide adenine dinucleotide (NAD+) metabolism is deregulated in cancer. Nicotinamide N-methyltransferase (NNMT) and aldehyde oxidase (AOX1) cooperatively protect cells from the negative effect of nicotinamide (NAM) accumulation in cells and its inhibitory effect on NAD+-dependent signaling reactions. Aberrantly elevated activity of NNMT and AOX1 may, over time, cause NAD+ depletion, mediated by exclusion of NAM from the NAD+ salvage pathway. To investigate NNMT and AOX1-mediated "NAM drain", various cancer cell lines were first tested for the expression of these two enzymes. Cell lines HT-29, Cal27, Detroit 562 and MDA-MB-231 were found to simultaneously express different levels of NNMT and AOX1 and were chosen for interrogation of the effect of raloxifene hydrochloride, a potent AOX1 inhibitor, on cellular NAD+ level. Tested cell lines differed in their basal cellular NAD+ level. Upon treatment with raloxifene hydrochloride, NAD+ level increased in all tested cell lines, but the extent of the increase was cell-type specific. Unexpectedly, dimethyl sulphoxide (DMSO) in concentration of 0.05%, used as raloxifene hydrochloride solvent, had profound negative effect on NAD+ level in HT-29, Cal27 and MDA-MB-231, but not Detroit 562 cells. The presented results warrant detailed further exploration of cell-type specific potency of raloxifene hydrochloride in restoring cellular NAD+ levels and the extent to which DMSO is blunting this effect in cell culture models.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
Prema pravilima UNIVERSITE GRENOBLE ALPES, rad je pisan u obliku znanstvenog članka

POVEZANOST RADA