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Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells
U Wenzel1, S Kuntz, M D Brendel
1Institute of Nutritional Sciences, University of Giessen, Germany. uwenzel@pollux.weihenstephan.de
Abstract:
Flavonoids are polyphenolic compounds that occur ubiquitously in plants. They are discussed to represent cancer preventive food components in a human diet that is rich in fruits and vegetables. To understand the molecular basis of the putative anticancer activity of flavonoids, we investigated whether and how the core structure of the flavones, 2-phenyl-4H-1-benzopyran-4-one (flavone) affects proliferation, differentiation, and apoptosis in HT-29 human colon cancer cells. Moreover, the effects of flavone in transformed epithelial cells were compared with those obtained in nontransformed primary mouse colonocytes. Proliferation, differentiation, and apoptosis in transformed as well as nontransformed colon cells were measured by fluorescence-based techniques. Apoptosis was also determined by changes in membrane permeability, FACScan analysis, and detection of DNA fragmentation. Semiquantitative reverse transcription PCR was performed to assess the effects of flavone on transcript levels. Flavone was found to reduce cell proliferation in HT-29 cells with an EC(50) value of 54.8 +/- 1.3 microM and to potently induce differentiation as well as apoptosis. The flavonoid proved to be a stronger apoptosis inducer than the clinically established antitumor agent camptothecin. The effects of flavone in HT-29 cells were associated with changed mRNA levels of cell-cycle- and apoptosis-related genes including cyclooxygenase-2 (COX-2), nuclear transcription factor kappaB (NF-kappaB), and bcl-X(L). Moreover, flavone, but not camptothecin, displayed a high selectivity for the induction of apoptosis and of growth inhibition only in the transformed colonocytes. In conclusion, the plant polyphenol flavone induces effectively programmed cell death, differentiation, and growth inhibition in transformed colonocytes by acting at the mRNA levels of genes involved in these processes. Because these genes play a crucial role in colon carcinogenesis, flavone may prove to be a potent new cytostatic compound with improved selectivity toward transformed cells.
Insights
The plant compound flavone effectively inhibits colon cancer cell growth, promoting cell death and differentiation. It shows selective action against transformed cells, offering potential as a targeted cancer therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Flavonoids are plant-derived polyphenols recognized for potential health benefits, including cancer prevention.
- The specific anticancer mechanisms of flavones, a subclass of flavonoids, require further elucidation at the molecular level.
Purpose of the Study:
- To investigate the effects of flavone on proliferation, differentiation, and apoptosis in human colon cancer cells (HT-29).
- To compare the actions of flavone in transformed colon cancer cells versus nontransformed primary mouse colonocytes.
- To explore the molecular pathways influenced by flavone, including gene expression changes.
Main Methods:
- Utilized fluorescence-based techniques to measure cell proliferation, differentiation, and apoptosis.
- Assessed apoptosis through membrane permeability changes, FACScan analysis, and DNA fragmentation detection.
- Employed semiquantitative reverse transcription PCR to analyze alterations in gene transcript levels.
Main Results:
- Flavone significantly reduced HT-29 cell proliferation (EC50: 54.8 µM) and potently induced differentiation and apoptosis.
- Flavone demonstrated superior apoptosis induction compared to the chemotherapeutic agent camptothecin.
- Selective induction of apoptosis and growth inhibition was observed in transformed colonocytes, but not in nontransformed cells.
- Flavone modulated mRNA levels of key genes, including cyclooxygenase-2 (COX-2), nuclear transcription factor kappaB (NF-kappaB), and bcl-X(L).
Conclusions:
- The plant polyphenol flavone effectively induces apoptosis, differentiation, and growth inhibition in transformed colonocytes.
- Flavone's mechanism involves altering the mRNA expression of genes critical to cell-cycle regulation and apoptosis.
- Flavone exhibits promising selectivity towards transformed colonocytes, suggesting its potential as a novel cytostatic agent for colon cancer treatment.