ReferenceID 5890
Oleanolic acid induces HCT116 colon cancer cell death through the p38/FOXO3a/Sirt6 pathway
Chem Biol Interact
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/mitoph
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 5890
- Evidence Id
- 22480
- Core Evidence Id
- 22480
- Source Reference Id
- 5047
- Herb2 Reference Id
- HBREF005844
- Subject Paper Key
- HBIN037940_35690101
- Pubmed Id
- 35690101
- Doi
- 10.1016/j.cbi.2022.110010
- Paper Title
- Oleanolic acid induces HCT116 colon cancer cell death through the p38/FOXO3a/Sirt6 pathway
- Paper Abstract
- 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 IC 50 = 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).
- Journal
- Chem Biol Interact
- Publish Year
- 2022
- Experiment Subject
- mouse; hct116 cell line; hct116 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Tumor; Colon Cancer
- Paper Title Cn
- Paper Title En
- Oleanolic acid induces HCT116 colon cancer cell death through the p38/FOXO3a/Sirt6 pathway
- Bilingual Status
- semi_complete