Naslov
Metabolism and differentiation

Autori
Višnjić, Dora ; Lalić, Hrvoje ; Dembitz, Vilma ; Banfić, Hrvoje

Izvornik
Periodicum biologorum (0031-5362) 116 (2014), 1; 37-43

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, ostalo

Ključne riječi
Metabolism ; Differentiation ; Leukemia

Sažetak
Textbook biochemical pathways do not usually apply to intermediary metabolism of highly proliferating, differentiating, or tumor cells. Over 80 years ago, Otto Warburg observed that cancer cells, unlike normal cells, favor glycolysis for energy production, even under aerobic conditions, and proposed that this shift in cancer cell metabolism (termed „aerobic glycolysis”) was due to mitochondrial dysfunction. Recent studies by several groups suggest that aerobic glycolysis in tumor cells is actually caused by oncogene-directed changes in metabolism that are necessary for both continuous proliferation and a block in cellular differentiation. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is one of the principal proliferative and anti-apoptotic signaling pathways, which is known to support glycolysis and anabolism. Our previous studies demonstrated the activation of PI3K and Akt in nuclei of leukemia cells during differentiation, and confirmed that the inhibition of proximal components of the pathway inhibits proliferation, but negatively affects differentiative capacity of the cells. In contrast, use of rapamycin, which inhibits mTOR, a more distal component of the pathway, potentiates differentiation along granulocytic pathway. To further investigate the role of upstream regulators of mTOR in leukemia differentiation, we tested the effects of modulators of AMP-activated protein kinase (AMPK). Our results suggest a strong differentiative property of an AMPK activator, AICAR (5-amino1-b-D-ribofuranosyl- imidazole-4-carboxamide) in monocytic U937 cells. The mechanism of AICAR-mediated effects will be presented and a possible role of AMPK-modulators in differentiation therapy will be discussed.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA