The Inhibitory Effect and Mechanism of the Histidine-Rich Peptide rAj-HRP from on Human Colon Cancer HCT116 Cells.
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| Autori principali: | , , , , , , , , |
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| Natura: | Artículo científico |
| Lingua: | en |
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Molecules (Basel, Switzerland)
2024
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| _version_ | 1868266282461167616 |
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| author | Zhang, Yuebin Gao, Shan Mao, Jiaming Song, Yuyao Wang, Xueting Jiang, Jingwei Lv, Li Zhou, Zunchun Wang, Jihong |
| author_facet | Zhang, Yuebin Gao, Shan Mao, Jiaming Song, Yuyao Wang, Xueting Jiang, Jingwei Lv, Li Zhou, Zunchun Wang, Jihong Zhang, Yuebin Gao, Shan Mao, Jiaming Song, Yuyao Wang, Xueting Jiang, Jingwei Lv, Li Zhou, Zunchun Wang, Jihong |
| collection | PubMed - marine biology |
| contents | The Inhibitory Effect and Mechanism of the Histidine-Rich Peptide rAj-HRP from on Human Colon Cancer HCT116 Cells. Zhang, Yuebin Gao, Shan Mao, Jiaming Song, Yuyao Wang, Xueting Jiang, Jingwei Lv, Li Zhou, Zunchun Wang, Jihong Humans Animals HCT116 Cells Colonic Neoplasms Cell Proliferation Apoptosis Mice Cell Movement Stichopus Xenograft Model Antitumor Assays Mice, Inbred BALB C Peptides Proteins Antineoplastic Agents Cell Adhesion Signal Transduction Histidine-Rich Glycoprotein Colon cancer is a common and lethal malignancy, ranking second in global cancer-related mortality, highlighting the urgent need for novel targeted therapies. The sea cucumber () is a marine organism known for its medicinal properties. After conducting a bioinformatics analysis of the cDNA library of , we found and cloned a cDNA sequence encoding histidine-rich peptides, and the recombinant peptide was named rAj-HRP. Human histidine-rich peptides are known for their anti-cancer properties, raising questions as to whether rAj-HRP might exhibit similar effects. To investigate whether rAj-HRP can inhibit colon cancer, we used human colon cancer HCT116 cells as a model and studied the tumor suppressive activity in vitro and in vivo. The results showed that rAj-HRP inhibited HCT116 cell proliferation, migration, and adhesion to extracellular matrix (ECM) proteins in vitro. It also disrupted the cytoskeleton and induced apoptosis in these cells. In vivo, rAj-HRP significantly inhibited the growth of HCT116 tumors in BALB/c mice, reducing tumor volume and weight without affecting the body weight of the tumor-bearing mice. Western blot analysis showed that rAj-HRP inhibited HCT116 cell proliferation and induced apoptosis by upregulating BAX and promoting PARP zymogen degradation. Additionally, rAj-HRP inhibited HCT116 cell adhesion and migration by reducing MMP2 levels. Further research showed that rAj-HRP downregulated EGFR expression in HCT116 cells and inhibited key downstream molecules, including AKT, P-AKT, PLCγ, P38 MAPK, and c-Jun. In conclusion, rAj-HRP exhibits significant inhibitory effects on HCT116 cells in both in vitro and in vivo, primarily through the EGFR and apoptosis pathways. These findings suggest that rAj-HRP has the potential as a novel targeted therapy for colon cancer. |
| format | Artículo científico |
| id | pubmed_39519855 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Molecules (Basel, Switzerland) |
| record_format | pubmed |
| spellingShingle | The Inhibitory Effect and Mechanism of the Histidine-Rich Peptide rAj-HRP from on Human Colon Cancer HCT116 Cells. Zhang, Yuebin Gao, Shan Mao, Jiaming Song, Yuyao Wang, Xueting Jiang, Jingwei Lv, Li Zhou, Zunchun Wang, Jihong Humans Animals HCT116 Cells Colonic Neoplasms Cell Proliferation Apoptosis Mice Cell Movement Stichopus Xenograft Model Antitumor Assays Mice, Inbred BALB C Peptides Proteins Antineoplastic Agents Cell Adhesion Signal Transduction Histidine-Rich Glycoprotein The Inhibitory Effect and Mechanism of the Histidine-Rich Peptide rAj-HRP from on Human Colon Cancer HCT116 Cells. Zhang, Yuebin Gao, Shan Mao, Jiaming Song, Yuyao Wang, Xueting Jiang, Jingwei Lv, Li Zhou, Zunchun Wang, Jihong Humans Animals HCT116 Cells Colonic Neoplasms Cell Proliferation Apoptosis Mice Cell Movement Stichopus Xenograft Model Antitumor Assays Mice, Inbred BALB C Peptides Proteins Antineoplastic Agents Cell Adhesion Signal Transduction Histidine-Rich Glycoprotein Colon cancer is a common and lethal malignancy, ranking second in global cancer-related mortality, highlighting the urgent need for novel targeted therapies. The sea cucumber () is a marine organism known for its medicinal properties. After conducting a bioinformatics analysis of the cDNA library of , we found and cloned a cDNA sequence encoding histidine-rich peptides, and the recombinant peptide was named rAj-HRP. Human histidine-rich peptides are known for their anti-cancer properties, raising questions as to whether rAj-HRP might exhibit similar effects. To investigate whether rAj-HRP can inhibit colon cancer, we used human colon cancer HCT116 cells as a model and studied the tumor suppressive activity in vitro and in vivo. The results showed that rAj-HRP inhibited HCT116 cell proliferation, migration, and adhesion to extracellular matrix (ECM) proteins in vitro. It also disrupted the cytoskeleton and induced apoptosis in these cells. In vivo, rAj-HRP significantly inhibited the growth of HCT116 tumors in BALB/c mice, reducing tumor volume and weight without affecting the body weight of the tumor-bearing mice. Western blot analysis showed that rAj-HRP inhibited HCT116 cell proliferation and induced apoptosis by upregulating BAX and promoting PARP zymogen degradation. Additionally, rAj-HRP inhibited HCT116 cell adhesion and migration by reducing MMP2 levels. Further research showed that rAj-HRP downregulated EGFR expression in HCT116 cells and inhibited key downstream molecules, including AKT, P-AKT, PLCγ, P38 MAPK, and c-Jun. In conclusion, rAj-HRP exhibits significant inhibitory effects on HCT116 cells in both in vitro and in vivo, primarily through the EGFR and apoptosis pathways. These findings suggest that rAj-HRP has the potential as a novel targeted therapy for colon cancer. |
| title | The Inhibitory Effect and Mechanism of the Histidine-Rich Peptide rAj-HRP from on Human Colon Cancer HCT116 Cells. |
| topic | Humans Animals HCT116 Cells Colonic Neoplasms Cell Proliferation Apoptosis Mice Cell Movement Stichopus Xenograft Model Antitumor Assays Mice, Inbred BALB C Peptides Proteins Antineoplastic Agents Cell Adhesion Signal Transduction Histidine-Rich Glycoprotein |
| url | https://pubmed.ncbi.nlm.nih.gov/39519855/ |