P53 is a transcriptional factor that plays important roles in apoptosis and is mutated in more than 50% of tumor cells. However, the restoration of mutated p53 to the level similar to wild-type p53 by a natural compound has not been explored intensively. In this study, the 2-[(4-hydroxybenzyl) amino] phenol (HBAP) compound, obtained from deep-sea virus-challenged thermophile Geobacillus sp. E263, interacted specifically with the mutated p53 protein. HBAP was able to induce apoptosis of p53-mutated breast cancer cells, but not normal breast cells and p53-unmutated breast cancer cells. HBAP activated the mutant p53 transcriptional activity by restoring the function of mutant p53 to that of wild-type p53. Further analysis indicated that HBAP bound only to the DNA binding domain of mutant p53 and that the interaction was dependent on the HBAP hydroxyl groups. In vivo data demonstrated that HBAP was toxicity-free and could suppress tumor growth by inducing tumor cell apoptosis. Therefore our findings revealed that recovering mutated p53 function to that of wild-type p53 caused by HBAP triggered cancer cell apoptosis and that metabolites from deep-sea virus-challenged thermophiles could be a promising source of anti-tumor drugs.
Objective In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL).Materials and methods The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment.Results After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05).Conclusions These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.
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