title: Anti-cancer effect of snake venom toxin through down regulation of AP-1 mediated PRDX6 expression.
abstract: Snake venom toxin (SVT) from Vipera lebetina turanica contains a mixture of different enzymes and proteins. Peroxiredoxin 6 (PRDX6) is known to be a stimulator of lung cancer cell growth. PRDX6 is a member of peroxidases, and has calcium-independent phospholipase A2 (iPLA2) activities. PRDX6 has an AP-1 binding site in its promoter region of the gene. Since AP-1 is implicated in tumor growth and PRDX6 expression, in the present study, we investigated whether SVT inhibits PRDX6, thereby preventing human lung cancer cell growth (A549 and NCI-H460) through inactivation of AP-1. A docking model study and pull down assay showed that SVT completely fits on the basic leucine zipper (bZIP) region of c-Fos of AP-1. SVT (0-10 μg/ml) inhibited lung cancer cell growth in a concentration dependent manner through induction of apoptotic cell death accompanied by induction of cleaved caspase-3, -8, -9, Bax, p21 and p53, but decreased cIAP and Bcl2 expression via inactivation of AP-1. In an xenograft in vivo model, SVT (0.5 mg/kg and 1 mg/kg) also inhibited tumor growth accompanied with the reduction of PRDX6 expression, but increased expression of proapoptotic proteins. These data indicate that SVT inhibits tumor growth via inhibition of PRDX6 activity through interaction with its transcription factor AP-1.
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Son
authors.affiliation: Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Gachon University, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii, Republic of Korea.
authors.forename: Ho Sueb
authors.initials: HS
authors.lastname: Song
authors.affiliation: Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Gachon University, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii, Republic of Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Gachon University, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii, Republic of Korea.
authors.forename: Seong Cheol
authors.initials: SC
authors.lastname: Ko
authors.affiliation: Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Jung-gu, Daejeon, Republic of Korea.
authors.forename: Min Jong
authors.initials: MJ
authors.lastname: Song
authors.affiliation: Department of Nuclear Medicine Chungbuk National University Hospital, Seowon, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Won Hyoung
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Paldal-gu, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Joo Hee
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA.
authors.forename: Young Wan
authors.initials: YW
authors.lastname: Ham
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D062105:Molecular Docking Simulation; D054465:Peroxiredoxin VI / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012910:Snake Venoms / Q000737:chemistry / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D012910:Snake Venoms; D018808:Transcription Factor AP-1; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI
keywords: AP-1; PRDX6; apoptosis; lung cancer; snake venom toxin