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豪猪刺角蛋白肽通过 p53/p21 通路和 caspase 级联反应诱导 MCF-7 乳腺癌细胞 G0/G1 期细胞周期阻滞和凋亡。

Porcupine quills keratin peptides induces G0/G1 cell cycle arrest and apoptosis via p53/p21 pathway and caspase cascade reaction in MCF-7 breast cancer cells.

机构信息

College of Food Science, South China Agricultural University, Guangzhou, China.

School of Chinese Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

J Sci Food Agric. 2024 Feb;104(3):1741-1755. doi: 10.1002/jsfa.13065. Epub 2023 Nov 8.

DOI:10.1002/jsfa.13065
PMID:37862230
Abstract

BACKGROUND

Porcupine quills, a by-product of porcupine pork, are rich in keratin, which is an excellent source of bioactive peptides. The objective of this study was to investigate the underlying mechanism of anti-proliferation effect of porcupine quills keratin peptides (PQKPs) on MCF-7 cells.

RESULTS

Results showed that PQKPs induced MCF-7 cells apoptosis by significantly decreasing the secretion level of anti-apoptosis protein Bcl-2 and increasing the secretion levels of pro-apoptosis proteins Bax, cytochrome c, caspase 9, caspase 3 and PARP. PQKPs also arrested the cell cycle at G0/G1 phase via remarkably reducing the protein levels of CDK4 and enhancing the protein levels of p53 and p21. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis identified nine peptides with molecular weights less than 1000 Da in PQKPs. Molecular docking results showed that TPGPPT and KGPAC identified from PQKPs could bind with p53 mutant and Bcl-2 protein by conventional hydrogen bonds, carbon hydrogen bonds and van der Waals force. Furthermore, the anti-proliferation impact of synthesized peptides (TPGPPT and KGPAC) was shown in MCF-7 cells.

CONCLUSION

These findings indicated that PQKPs suppressed the proliferation of MCF-7 breast cancer cells by triggering apoptosis and G0/G1 cell cycle arrest. Moreover, the outcome of this study will bring fresh insights into the production and application of animal byproducts. © 2023 Society of Chemical Industry.

摘要

背景

豪猪刺是豪猪肉的副产品,富含角蛋白,是生物活性肽的极好来源。本研究旨在探讨豪猪刺角蛋白肽(PQKPs)对 MCF-7 细胞的抗增殖作用的潜在机制。

结果

结果表明,PQKPs 通过显著降低抗凋亡蛋白 Bcl-2 的分泌水平和增加促凋亡蛋白 Bax、细胞色素 c、caspase 9、caspase 3 和 PARP 的分泌水平,诱导 MCF-7 细胞凋亡。PQKPs 还通过显著降低 CDK4 蛋白水平和增强 p53 和 p21 蛋白水平,将细胞周期阻滞在 G0/G1 期。高效液相色谱-串联质谱(HPLC-MS/MS)分析鉴定出 PQKPs 中 9 种分子量小于 1000Da 的肽。分子对接结果表明,从 PQKPs 中鉴定出的 TPGPPT 和 KGPAC 可通过常规氢键、碳氢键和范德华力与 p53 突变体和 Bcl-2 蛋白结合。此外,合成肽(TPGPPT 和 KGPAC)在 MCF-7 细胞中的抗增殖作用也得到了证实。

结论

这些发现表明,PQKPs 通过触发细胞凋亡和 G0/G1 细胞周期阻滞抑制 MCF-7 乳腺癌细胞的增殖。此外,本研究的结果将为动物副产品的生产和应用带来新的见解。© 2023 化学工业协会。

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