Flavonoids activate wild-type p53.
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.
Plaumann
B
B
Abteilung Virologie, Institut für Medizinische Mikrobiologie and Hygiene der Universität, Frieburg, Germany.
Fritsche
M
M
Rimpler
H
H
Brandner
G
G
Hess
R D
RD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D005419:Flavonoids / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008938:Mitosis / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D005419:Flavonoids; D016159:Tumor Suppressor Protein p53