Naslov
Oleanolic acid induces HCT116 colon cancer cell death through the p38/FOXO3a/Sirt6 pathway

Autori
Potočnjak, Iva ; Šimić, Lidija ; Vukelić, Iva ; Batičić, Lara ; Domitrović, Robert

Izvornik
Chemico-Biological Interactions (0009-2797) 363 (2022); 110010, 11

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
oleanolic acid ; colon cancer ; apoptosis ; autophagy ; mitophagy ; 5-fluorouracil

Sažetak
Oleanolic acid (OA) is a natural compound that possesses numerous beneficial health effects, including anticancer activity. The current study aimed to investigate the role of forkhead box O3a (FOXO3a) in autophagy/mitophagy by OA in HCT116 cell line. OA dose-dependently reduced viability of HCT116 cells, with IC50 = 29.8 μΜ. The expression of cleaved caspase-3 and poly (ADP- ribose) polymerase 1 increased after OA treatment, suggesting induction of apoptosis. Concurrently, OA induced autophagy, evidenced by increased expression of Beclin-1, autophagy-related protein 5 and microtubule-associated protein1A/1B-light chain 3 beta (LC3B), which played a prosurvival role. The induction of mitophagy was suggested by increased expression of p62 and PTEN-induced kinase 1 and reduced expression of translocase of outer mitochondrial membrane 20, which colocalized with LC3B. OA also induced nuclear accumulation of forkhead box O3a (FOXO3a). The cytotoxic activity of OA coincided with upregulation of p38. Inhibition of p38 led to increase in FOXO3a and NAD+- dependent deacetylase sirtuin 6 expression. In vivo, OA inhibited tumor growth in colon cancer xenograft mice. Our results suggest concomitant induction of apoptosis and prosurvival mitophagy by OA in colon cancer via p38/FOXO3a/Sirt6 signaling. Additionally, our data demonstrate that OA can chemosensitize colon cancer cells to 5- fluorouracil (5-FU).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA