Abstract |
Based on the three-dimensional modeling structure of human interleukin-24 (hIL-24) and its most likely active position predicted by solvent accessibility and apparent electrostatic properties, a novel hIL-24 peptide M1 was created by computer-guided molecular design. The cytotoxicity and cell selectivity of M1 were examined in three human carcinoma cell lines and one normal human embryo lung fibroblast cell line (HEL). MTT assay showed that M1 induced growth arrest in two IL-20 receptor complex-positive cancer cell lines (the esophageal squamous cell carcinoma cell line Eca-109 and the melanoma cell line A375), and antibodies against IL-24 or IL-20 receptor complexes significantly neutralized the inhibitory activity. Moreover, M1 had almost no cytotoxicity on the lung cancer A549 cell line, which lacks a full complement of the IL-20 receptor complexes, or on HEL cells that express the IL-20 receptor complexes. These findings demonstrate that M1 could act as an excellent candidate for the induction of growth arrest on receptor complex-positive cancer cells. In summary, the M1 peptide may represent a novel anticancer agent for esophageal squamous cell carcinoma therapy due to its cancer cell selectivity and its relatively low cytotoxicity to normal cells.
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Authors | Qunfeng Ma, Xuefeng Deng, Bangming Jin, Yao Zhang, Dan Luo, Heyu Song, Pengkun Wang, Chi Zhang, Xue Li, Yinan Shi, Yan Liu, Zhinan Chen, Ziling Wang, Hong Jiang |
Journal | Oncology reports
(Oncol Rep)
Vol. 33
Issue 1
Pg. 193-200
(Jan 2015)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 25371158
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Interleukins
- interleukin-24
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Topics |
- Antineoplastic Agents
(chemical synthesis, pharmacology)
- Carcinoma, Squamous Cell
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Computer-Aided Design
- Drug Design
- Esophageal Neoplasms
- Esophageal Squamous Cell Carcinoma
- Humans
- Inhibitory Concentration 50
- Interleukins
(chemical synthesis, pharmacology)
- Models, Molecular
- Protein Conformation
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