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Flavonoids activate wild-type p53
B Plaumann1, M Fritsche, H Rimpler
1Abteilung Virologie, Institut für Medizinische Mikrobiologie and Hygiene der Universität, Frieburg, Germany.
Abstract:
Flavonoids are diphenyl propanoids widely distributed in edible plants. They play a dual role in mutagenesis and carcinogenesis. Some of them act as anticarcinogens or inhibit the growth of tumour cells, whereas others act as cocarcinogens, are mutagenic or able to induce DNA damage. To further elucidate this dual role, we investigated the influence of apigenin, luteolin and quercetin on the tumour suppressor protein p53, regarding p53 accumulation, cell cycle arrest, apoptosis, and biological activity. We found that incubation of the non-tumour cell line C3H10T1/2CL8 with these flavonoids resulted in induction of p53 accumulation and apoptosis. Apoptosis occurred out of the G2/M phase of the cell cycle. The G2/M arrest seems to be p53-dependent as it did not occur in p53 knockout fibroblasts which further supports the recent finding that p53 is involved in the G2/M checkpoint control. Differences between the flavonoids tested concerned p53 accumulation kinetics as well as the biological activity of accumulated p53 and might be due to different modes of flavonoid action. These data suggest that both aspects of flavonoid effects, i.e. inhibition of tumour growth through cell cycle arrest and induction of apoptosis, are functionally related to p53.
Insights
Flavonoids like apigenin, luteolin, and quercetin induce tumor suppressor protein p53 accumulation and apoptosis in cells. This suggests a p53-dependent role for flavonoids in controlling cell cycle arrest and tumor growth inhibition.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Flavonoids, found in edible plants, exhibit a dual role in cancer, acting as both anticarcinogens and potential carcinogens.
- Their influence on cellular processes like mutagenesis and carcinogenesis necessitates further investigation.
Purpose of the Study:
- To investigate the impact of specific flavonoids (apigenin, luteolin, quercetin) on the tumor suppressor protein p53.
- To elucidate the effects on p53 accumulation, cell cycle arrest, apoptosis, and biological activity.
Main Methods:
- Incubation of non-tumour cell line C3H10T1/2CL8 with apigenin, luteolin, and quercetin.
- Analysis of p53 accumulation, cell cycle progression, and apoptosis induction.
- Comparison with p53 knockout fibroblasts to assess p53 dependency.
Main Results:
- Flavonoid treatment induced p53 accumulation and apoptosis in C3H10T1/2CL8 cells.
- Apoptosis occurred outside the G2/M phase, and G2/M arrest was found to be p53-dependent.
- Observed differences in p53 accumulation kinetics and biological activity among the tested flavonoids.
Conclusions:
- The tumor suppressor protein p53 is functionally linked to flavonoid-induced cell cycle arrest and apoptosis.
- Flavonoids' effects on inhibiting tumor growth and inducing apoptosis are mediated through p53.
- The study highlights the complex, p53-mediated mechanisms underlying flavonoid actions in cancer research.