title: Melittin suppresses EGF-induced cell motility and invasion by inhibiting PI3K/Akt/mTOR signaling pathway in breast cancer cells.
abstract: Bee venom is a natural compound produced by the honey bee (Apis mellifera), and has been reported as having the biological and pharmacological activities, including anti-bacterial, anti-viral and anti-inflammation. In the present study, the inhibitory effects of bee venom and its major peptide components on the tumor invasion were demonstrated. It was confirmed the inhibitory effects of bee venom, melittin, and apamin on the EGF-induced invasion of breast cancer cells. Transwell invasion and wound-healing assays showed that bee venom and melittin significantly inhibits the EGF-induced invasion and migration of breast cancer cells. Also, bee venom and melittin reduced the EGF-stimulated F-actin reorganization at the leading edge, but apamin did not affect. Particularly, melittin inhibited the EGF-induced MMP-9 expression via blocking the NF-κB and PI3K/Akt/mTOR pathway. In addition, melittin significantly suppressed the EGF-induced FAK phosphorylation through inhibition of mTOR/p70S6K/4E-BP1 pathway. These results suggest that inhibitory effects of melittin on breast cancer cell motility and migration may be related to the inhibition of mTOR pathway.
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: National Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.
authors.forename: Yongsoo
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus program), Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Jae-Moon
authors.initials: JM
authors.lastname: Shin
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Choe
authors.affiliation: School of Life Sciences, KNU Creative BioResearch Group (BK21 plus program), Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
authors.affiliation: Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon, Kyunggi-Do 441-100, Republic of Korea.
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Han
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Kyunggi-Do 440-746, Republic of Korea.
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 701-947, Republic of Korea.
authors.forename: Hyeun-Wook
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea. Electronic address: ycchang@cu.ac.kr.
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008555:Melitten / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D004815:Epidermal Growth Factor; D051417:Focal Adhesion Kinase 1; D020780:Matrix Metalloproteinase 9; D008555:Melitten; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C496050:PTK2 protein, human; C579270:MMP9 protein, human
keywords: Bee venom; Cancer invasion; FAK; MMP; Melittin