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Naringenin-Mediated ATF3 Expression Contributes to Apoptosis in Human Colon Cancer
Hun Min Song1, Gwang Hun Park1, Hyun Ji Eo1
1Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
Abstract:
Naringenin (NAR) as one of the flavonoidsobserved in grapefruit has been reported to exhibit an anti-cancer activity. Activating transcription factor 3 (ATF3) is associated with apoptosis in human colon cancer cells. This study was performed to investigate the molecular mechanism by which NAR stimulates ATF3 expression and apoptosis in human colon cancer cells. NAR reduced the cell viability and induced an apoptosis in human colon cancer cells. ATF3 overexpression increased NAR-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by NAR. NAR increased ATF3 expression in both protein and mRNA level, and increased the luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by NAR is located between -317 and -148 of ATF3 promoter. p38 inhibition blocked NAR-mediated ATF3 expression, its promoter activation and apoptosis. The results suggest that NAR induces apoptosis through p38-dependent ATF3 activation in human colon cancer cells.
Insights
Naringenin (NAR), a grapefruit flavonoid, induces apoptosis in human colon cancer cells by activating the transcription factor 3 (ATF3) via the p38 pathway. This mechanism enhances cancer cell death.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Naringenin (NAR), a flavonoid found in grapefruit, shows potential anti-cancer properties.
- Activating transcription factor 3 (ATF3) plays a role in apoptosis in human colon cancer cells.
Purpose of the Study:
- To investigate the molecular mechanism of NAR-induced ATF3 expression and apoptosis in human colon cancer cells.
- To elucidate the role of the p38 pathway in NAR's anti-cancer effects.
Main Methods:
- Cell viability assays and apoptosis detection.
- Western blotting and qRT-PCR to assess protein and mRNA levels of ATF3.
- Luciferase reporter assays to analyze ATF3 promoter activity.
- Pharmacological inhibition of the p38 pathway.
Main Results:
- NAR reduced colon cancer cell viability and induced apoptosis.
- NAR dose-dependently increased ATF3 expression and promoter activity.
- ATF3 overexpression enhanced NAR-mediated PARP cleavage, while knockdown attenuated it.
- p38 pathway inhibition blocked NAR-induced ATF3 expression, promoter activation, and apoptosis.
Conclusions:
- Naringenin induces apoptosis in human colon cancer cells.
- The mechanism involves the activation of ATF3 expression via the p38 signaling pathway.
- NAR represents a potential therapeutic agent for colon cancer.
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