Inhibitory effect of snake venom toxin on NF-kappa B activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression
- Authors
- Lee, Hye Lim; Park, Mi Hee; Hong, Ji Eun; Kim, Dae Hwan; Kim, Ji Young; Seo, Hyen Ok; Han, Sang-Bae; Yoon, Joo Hee; Lee, Won Hyoung; Song, Ho Sueb; Lee, Ji In; Lee, Ung Soo; Song, Min Jong; Hong, Jin Tae
- Issue Date
- Feb-2016
- Publisher
- SPRINGER HEIDELBERG
- Keywords
- Snake venom toxin; Apoptosis; Death receptors; NF-kappa B; Cervical cancer
- Citation
- ARCHIVES OF TOXICOLOGY, v.90, no.2, pp.463 - 477
- Journal Title
- ARCHIVES OF TOXICOLOGY
- Volume
- 90
- Number
- 2
- Start Page
- 463
- End Page
- 477
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8633
- DOI
- 10.1007/s00204-014-1393-5
- ISSN
- 0340-5761
- Abstract
- We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-kappa B) activity in several cancer cells. NF-kappa B is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-kappa B, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 mu g/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-kappa B activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-kappa B inhibitor (Phenylarsine oxide, 0.1 mu M) 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-kappa B 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-kappa B, 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-kappa B. 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.
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