title: Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression.
abstract: We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 μg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 μM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Hong
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.
authors.forename: Hyen Ok
authors.initials: HO
authors.lastname: Seo
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 93 Jungbu-Daero, Paldal-gu, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Joo Hee
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Nuclear Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea.
authors.forename: Won Hyoung
authors.initials: WH
authors.lastname: Lee
authors.affiliation: College of Oriental Medicine, Gachon University, San 65, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggi-do, 461-701, Republic of Korea.
authors.forename: Ho Sueb
authors.initials: HS
authors.lastname: Song
authors.affiliation: College of Oriental Medicine, Gachon University, San 65, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggi-do, 461-701, Republic of Korea.
authors.forename: Ji In
authors.initials: JI
authors.lastname: Lee
authors.affiliation: Department of Food Science and Technology, Korea National University of Transportation, 61 Daehak-ro, Jeungpyeong-gun, Chungbuk, 368-701, Republic of Korea.
authors.forename: Ung Soo
authors.initials: US
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon, Republic of Korea. bitsugar@hanmail.net.
authors.forename: Min Jong
authors.initials: MJ
authors.lastname: Song
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 316-200, Republic of Korea. jinthong@chungbuk.ac.kr.|College of Pharmacy, Medical Research Center, Chungbuk National University, 52, Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea. jinthong@chungbuk.ac.kr.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001152:Arsenicals / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014757:Viper Venoms / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001152:Arsenicals; D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C506033:TNFRSF25 protein, human; D014757:Viper Venoms; C029341:oxophenylarsine
keywords: Apoptosis; Cervical cancer; Death receptors; NF-κB; Snake venom toxin