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Inhibitory effect and mechanism of Bursal-derived pentapeptide-Ⅱ on tumor cell proliferation and its possible medanism
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Abstract:
Objectiv : To study the anti-tumor activity and mechanism of Bursal-derived pentapeptide-Ⅱ(BPP-Ⅱ). Methods: Tumor cells including murine B-cell lymphoma WEHI-231 cells, human nasopharyngeal carcinoma CNE cells and rat hepatoma RH-35 cells and normal cells including human embryonic kidney 293 cells, pig kidney PK15 cells and Chinese hamster ovary CHO cells were stimulated with BPP-Ⅱ at 0.02 μg/ml, 0.2 μg/ml, 2 μg/ml and 20 μg/ml for 48 h. Cell viability was then measured by MTT assays, p53 luciferase activity and the expression of P53 at the protein level were assessed, and the effect of BPP-Ⅱ binding peptides biopaned from a phage display 12-mer random peptide library on BPP-Ⅱ-mediated inhibition of WEHI-231 cell proliferation was determined by MTT assays. Results: BPP-Ⅱ inhibited the proliferation of tumor cells but not normal cells, activated p53 transcription, and increased P53 protein content. After four rounds of biopanning, three BPP-Ⅱ binding peptides were obtained: QSLPSPLWIQQS (P3-12), DRMPDSAWTTRK (P5-12) and ALWPPNLHAWVP (P6-12). P3-12 significantly inhibited the anti-proliferative activity of BPP-Ⅱ at both 2 μg/ml (97.5±3.4)% and 20 μg/ml (98.9±3.5)% as compared with the control (86.3±1.9)% in WEHI-231 cells (P<0.05). At 20 μg/ml, both P5-12 (96.7±3.1)% and P6-12 (95.4±3.8)% inhibited the anti-proliferative activity of BPP-Ⅱ as compared with the control (86.3±1.9%) in WEHI-231 cells (P<0.05). Conclusions: BPP-Ⅱ appears to have an antitumor activity, possibly attributable to p53 activation. Taken together, our findings suggest a significant clinical importance for BPP-Ⅱ from the perspective of cancer therapy.
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Project Supported:
Projects supported by the National Natural Science Foundation for Young Scientists of China（No.31101792, No.31201928）, and the Foundation for the Young Core Instructor from the Higher Education of Henan Province（No.2012GGJS-07）
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