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 the m act as anticarcinogens or inhibit the growth of tumour cells, wherea s others act as cocarcinogens, are mutagenic or able to induce DNA dam age. To further elucidate this dual role, we investigated the influenc e of apigenin, luteolin and quercetin on the tumour suppressor protein p53, regarding p53 accumulation, cell cycle arrest, apoptosis, and bi ological activity. We found that incubation of the non-tumour cell lin e C3H10T1/2CL8 with these flavonoids resulted in induction of p53 accu mulation and apoptosis. Apoptosis occurred out of the G(2)/M phase of the cell cycle, The G(2)/M arrest seems to be p53-dependent as it did not occur in p53 knockout fibroblasts which further supports the recen t finding that p53 is involved in the G(2)/M checkpoint control. Diffe rences between the flavonoids tested concerned p53 accumulation kineti cs as well as the biological activity of accumulated p53 and might be due to different modes of flavonoid action. These data suggest that bo th aspects of flavonoid effects, i.e. inhibition of tumour growth thro ugh cell cycle arrest and induction of apoptosis, are functionally rel ated to p53.