title: The study of a novel sorafenib derivative HLC-080 as an antitumor agent.
abstract: In this study, our objective is to evaluate the potential of a novel Sorafenib derivative, named HLC-080, as a new anticancer agent for colon cancer. We firstly carried out MTT assay, colony formation assay, flow cytometry analysis and transwell invasion assay to determine effect of our compound HLC-080 on cell viability, anti-proliferation activity, cell cycle arrest and the intervention on cell invasion, respectively. On the other hand, in vivo antitumor activity of HLC-080 was also tested using H22 xenograft model and the angiogenesis effect of HLC-080 was measured by EA.hy926 tube formation assay. The expression levels of various proteins in HLC-080 treated with HT-29 cell lines were examined using Western blot and ELISA experiments. The results showed that HLC-080 could dramatically inhibit the growth and colony formation of various tumor cells, therefore exhibited remarkable antitumor activity. HLC-080 can induce cell cycle arrest at G1 phase in HT-29 cells and subsequently inhibit the invasive potential of colon cancer cells. HLC-080 also exhibits anti-angiogenesis effect in EA.hy926 model. Additionally, the in vivo study showed that HLC-080 was able to reduced the tumor weight with the rate of 35.81%. And at the concentration of 0.352±0.034 µM, HLC-080 is able to reduce half of the regular protein level of p-c-Raf (Ser259), consequently block Raf/MEK/ERK signaling in HT-29 cell lines. In conclusion, our study suggests that Sorafenib derivative HLC-080 has the potential to inhibit cell proliferation and angiogenesis, Since, HLC-080 is particularly active against human colon cancer cells, our study highlights that HLC-080 and its related analogues may serve as a new anti-cancer drug, particularly against colon cancer.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Can
authors.initials: C
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Chenshu
authors.initials: C
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Wanqi
authors.initials: W
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010671:Phenylurea Compounds / Q000494:pharmacology*; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C000602090:HLC-080; D010671:Phenylurea Compounds; D013449:Sulfonamides; D019908:Proto-Oncogene Proteins c-raf