title: Anti-tumoral effect of the mitochondrial target domain of Noxa delivered by an engineered Salmonella typhimurium.
abstract: Bacterial cancer therapy relies on the fact that several bacterial species are capable of targeting tumor tissue and that bacteria can be genetically engineered to selectively deliver therapeutic proteins of interest to the targeted tumors. However, the challenge of bacterial cancer therapy is the release of the therapeutic proteins from the bacteria and entry of the proteins into tumor cells. This study employed an attenuated Salmonella typhimurium to selectively deliver the mitochondrial targeting domain of Noxa (MTD) as a potential therapeutic cargo protein, and examined its anti-cancer effect. To release MTD from the bacteria, a novel bacterial lysis system of phage origin was deployed. To facilitate the entry of MTD into the tumor cells, the MTD was fused to DS4.3, a novel cell-penetrating peptide (CPP) derived from a voltage-gated potassium channel (Kv2.1). The gene encoding DS4.3-MTD and the phage lysis genes were placed under the control of PBAD , a promoter activated by L-arabinose. We demonstrated that DS4.3-MTD chimeric molecules expressed by the Salmonellae were anti-tumoral in cultured tumor cells and in mice with CT26 colon carcinoma.
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Kwangsoo
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Daejin
authors.initials: D
authors.lastname: Lim
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Kwangjoon
authors.initials: K
authors.lastname: Jeong
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Yeongjin
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Vu H
authors.initials: VH
authors.lastname: Nguyen
authors.affiliation: Department of Biochemistry, Chosun University Medical School, Gwangju, Republic of Korea.
authors.forename: Tae-Hyoung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Food and Animal Biotechnology, Seoul National University, Seoul, Korea.
authors.forename: Sangryeol
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Food and Animal Biotechnology, Seoul National University, Seoul, Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Lim
authors.affiliation: School of Life Science, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Yongbong-Dong, Buk-Gu, Gwangju, Korea.
authors.forename: Geun-Joong
authors.initials: GJ
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Sun Chang
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Hyon E
authors.initials: HE
authors.lastname: Choy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001089:Arabinose / Q000494:pharmacology; D001433:Bacteriolysis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry*; D012486:Salmonella typhimurium / Q000235:genetics*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D001089:Arabinose