The radioprotective effect of BBI is associated with the activation of DNA repair-relevant genes

Kh, Dittmann; Gueven, Nuri; Mayer, Claus; Hp, Rodemann

doi:10.1080/095530098141609

Cited by 27 publications

(19 citation statements)

References 24 publications

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“…Moreover, similar effects of P-Tyr and BBI could be identified by quantifying TP53 and CDKN1A protein levels after a preincubation with P-Tyr. As described for BBI [15], P-Tyr treatment also induced a significant stabilization of the TP53-protein in normal cells within 3 hr. Thus, the radioprotective effect of P-Tyr can be correlated with TP53 stabilization.…”

Section: Discussionsupporting

confidence: 65%

“…Although the mechanism of radioprotection mediated by P-Tyr is not clear at present, we favor an analogy to the mechanism described for BBI [15], a stimulating effect on DNA-repair processes.…”

Section: Discussionsupporting

confidence: 61%

“…The observed correlation between the P-Tyr-mediated radioprotection and TP53 function suggested an effect of P-Tyr on TP53 protein during the preincubation period before irradiation, as described previously for the Bowman-Birk protease inhibitor (BBI) [15]. To elucidate this correlation, normal fibroblasts and transformed cell lines with wild-type and mutated TP53 were incubated with P-Tyr for several time intervals and the protein levels of TP53 and CDKN1A were quantified (Fig.…”

Section: Effect Of P-tyr On Tp53-stabilization and Cdkn1a Protein Expsupporting

confidence: 63%

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O-phospho-L-tyrosine protects TP53 wild-type cells against ionizing radiation

2001

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SUMMARY O-phospho-L-tyrosine (P-Tyr) has been reported previously to inhibit growth of several cancer cell lines at mM concentrations. In the present study, we investigated the effect of this compound on tumor cells and normal cells in combination with radiation exposure. It could be demonstrated for the first time that P-Tyr at M concentrations protects TP53 wild-type cells against ionizing radiation (SF4 minus BBI ‫؍‬ 0.28, SF4 plus BBI ‫؍‬ 0.45). On the contrary, human transformed or tumor cell lines characterized by mutated or functional inactivated TP53 were not altered or increased in their radiation sensitivity (SF4 minus BBI ‫؍‬ 0.32, SF4 plus BBI ‫؍‬ 0.22). Treatment of wild-type TP53 cells with P-Tyr induced stabilization of TP53 within 3 and 16 hours and a subsequent increase in CDKN1A expression after treatment. Consequently, a 16-hours pretreatment of cells with P-Tyr led to a significant radioprotective effect. This was not observed in cell lines with mutated TP53, which shows no radioprotection by P-Tyr. Thus, the present data suggest that P-Tyr-mediated radioprotection is dependent on preirradiation stabilization of TP53. The results indicate that P-Tyr is a radioprotective agent that can potentially be very useful and easy to deliver for radiation protection in general and especially in radiation therapy of TP53-mutated tumors.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionsupporting

confidence: 61%

Section: Effect Of P-tyr On Tp53-stabilization and Cdkn1a Protein Expsupporting

confidence: 63%

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O-phospho-L-tyrosine protects TP53 wild-type cells against ionizing radiation

2001

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“…Purified soybean BBI and BBIC have been shown to inhibit the growth of LNCaP human prostate cancer xenografts in nude mice [72], and to decrease the growth, invasion and clonogenic survival of several human prostate cancer cells [73]. The effectiveness of soybean BBI in preventing the generation of activated oxygen species in prostate cancer cells [74] and in activating DNA repair through a p53-dependent mechanism has been reported [75]. More recently, BBIC has prevented the growth of prostate tumors in transgenic rats developing adenocarcinoma, most likely as a consequence of its antiproliferative activity via induction of connexin 43 expression [76,77].…”

Section: Prostate Cancermentioning

confidence: 99%

“…Dittmann et al [81] showed that soybean BBI increased clonogenic survival after irradiation only in cells, either normal or transformed, having a wild-type p53 tumor suppressor gene. In a cell line with inducible expression of mutated p53, the radioprotective effect of BBI was only detected when the expression of the mutated p53 was switched off [75]. The activation of the DNA-repair machinery, induced by pre-treatment of fibroblastic cells with soybean BBI, suggests a possible BBI-mediated p53-dependent mechanism for radioprotection [82,83].…”

Section: Radioprotectionmentioning

confidence: 99%