title: Structure-based design of peptides against HER2 with cytotoxicity on colon cancer.
abstract: In this study, we found that four novel peptides designed by molecular modeling techniques were successfully applicated with cytotoxicity on colon cancer cells sw620. First, the interactions between the Herstatin and the HER2 were explored by ational-designed approaches, which were combined with homology modeling, protein/protein docking, and structural superimposition analysis. Then, based on the results derived from theoretical analysis, four novel peptides were designed, synthesized, and experimentally evaluated for biological function; it was found that they showed a remarkable enhancement on Herceptin to inhibit the genesis and development of colon cancers, and no significant side effects on normal colon cells NCM460 were observed but Doxorubicin had. These results indicated that it is a feasible way to use the well-designed peptides derived from Herstatin to enhance the efficacy of clinical drugs Herceptin and to kill colon cancer cells selectively without harming normal colon cells. We believe that our research might provide a new way to develop the potential therapies for colon cancers.
authors.affiliation: a Cancer Center, Beijing Key Lab of Therapeutic Cancer Vaccines , Beijing Shijitan Hospital, Capital Medical University , Beijing , P.R. China.|b Department of Surgical Oncology , Inner Mongolia People's Hospital , Hohhot , Inner Mongolia , P.R. China.
authors.forename: Nier
authors.initials: N
authors.lastname: Cha
authors.affiliation: b Department of Surgical Oncology , Inner Mongolia People's Hospital , Hohhot , Inner Mongolia , P.R. China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Han
authors.affiliation: b Department of Surgical Oncology , Inner Mongolia People's Hospital , Hohhot , Inner Mongolia , P.R. China.
authors.forename: Baoqing
authors.initials: B
authors.lastname: Jia
authors.affiliation: b Department of Surgical Oncology , Inner Mongolia People's Hospital , Hohhot , Inner Mongolia , P.R. China.
authors.forename: Yanheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Cancer Center, Beijing Key Lab of Therapeutic Cancer Vaccines , Beijing Shijitan Hospital, Capital Medical University , Beijing , P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: b Department of Surgical Oncology , Inner Mongolia People's Hospital , Hohhot , Inner Mongolia , P.R. China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: a Cancer Center, Beijing Key Lab of Therapeutic Cancer Vaccines , Beijing Shijitan Hospital, Capital Medical University , Beijing , P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D015195:Drug Design; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C434665:herstatin; C508053:ERBB2 protein, human
keywords: Colon cancer; Herstatin; peptide; rational design; target therapy