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4-O-Methylascochlorin Synergistically Enhances 5-Fluorouracil-Induced Apoptosis by Inhibiting the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer Cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 May 25; Vol. 25 (11). Date of Electronic Publication: 2024 May 25. - Publication Year :
- 2024
-
Abstract
- 4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin extracted from the fungus Ascochyta viciae , shows anticarcinogenic effects on various cancer cells. 5-Fluorouracil (5-FU) is used to treat colorectal cancer (CRC); however, its efficacy must be enhanced. In this study, we investigated the molecular mechanisms by which MAC acts synergistically with 5-FU to inhibit cell proliferation and induce apoptosis in CRC cells. MAC enhanced the cytotoxic effects of 5-FU by suppressing the Akt/mTOR/p70S6K and Wnt/β-catenin signaling pathways. It also reduced the viability of 5-FU-resistant (5-FU-R) cells. Furthermore, expression of anti-apoptosis-related proteins and cancer stem-like cell (CSC) markers by 5-FU-R cells decreased in response to MAC. Similar to MAC, the knockdown of CTNNB1 induced apoptosis and reduced expression of mRNA encoding CRC markers in 5-FU-R cells. In summary, these results suggest that MAC and other β-catenin modulators may be useful in overcoming the 5-FU resistance of CRC cells.
- Subjects :
- Humans
Cell Line, Tumor
Drug Resistance, Neoplasm drug effects
TOR Serine-Threonine Kinases metabolism
Fluorouracil pharmacology
Colorectal Neoplasms metabolism
Colorectal Neoplasms drug therapy
Colorectal Neoplasms pathology
Wnt Signaling Pathway drug effects
Apoptosis drug effects
Drug Synergism
beta Catenin metabolism
beta Catenin genetics
Cell Proliferation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 38891932
- Full Text :
- https://doi.org/10.3390/ijms25115746