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Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor κB and signal transducer and activator of transcription 3

Archives of Pharmacal Research volume 35, pages 867–876 (2012)Cite this article

Abstract

Snake venom toxin from Vipera lebetina turanica induces apoptosis in many cancer cell lines, but there is no study about the apoptotic effect of snake venom toxin on human ovarian cancer cells. In this study, we investigated the apoptotic effect of snake venom toxin in human ovarian cancer PA-1 and SK-OV3 cells. Snake venom toxin dose dependently (0∼10 μg/mL) inhibited ovarian cancer cell growth with IC50 values 4.5 μg/mL in PA-1 cells, and 6.5 μg/mL in SK-OV3 cells. Our results also showed that apoptotic cell death increased by snake venom toxin in a dose dependent manner (0∼10 μg/mL). Consistent with increased cell death, snake venom toxin increased the expression of pro-apoptotic protein Bax and caspase-3, but down-regulated anti-apoptotic protein Bcl-2. Untreated ovarian cancer cells showed a high DNA binding activity of nuclear factor B (NF-κB), but it was inhibited by snake venom toxin accompanied by inhibition of p50 and p65 translocation into the nucleus as well as phosphorylation of inhibitory κB. Snake venom toxin also inhibited DNA binding activity of the signal transducer and activator of transcription 3 (STAT3). Moreover, the combination treatment of NF-κB (salicylic acid, 1 or 5 μM) and STAT3 (stattic, 1 μM) with snake venom toxin (1 μg/mL) further enhanced cell growth inhibitory effects of snake venom toxin. These results showed that snake venom toxin from Vipera lebetina turanica caused apoptotic cell death of ovarian cancer cells through the inhibition of NF-κB and STAT3 signal, and suggested that snake venom toxin may be applicable as an anticancer agent for ovarian cancer.

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Affiliations

  1. College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 361-763, Korea

    Ju Kyoung Song, Mi Ran Jo, Mi Hee Park, Sang Bae Han & Jin Tae Hong

  2. College of Oriental Medicine, Kyungwon University, Seongnam, 461-701, Korea

    Ho Sueb Song & Byeong Jun An

  3. Obstetrics and Gynecology, SEOUL ST.MARY’s HOSPITAL, The Catholic University, Seoul, 137-040, Korea

    Min Jong Song

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  1. Ju Kyoung Song
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  2. Mi Ran Jo
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  3. Mi Hee Park
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  4. Ho Sueb Song
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  6. Min Jong Song
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  7. Sang Bae Han
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  8. Jin Tae Hong
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Correspondence to Jin Tae Hong.

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Song, J.K., Jo, M.R., Park, M.H. et al. Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor κB and signal transducer and activator of transcription 3. Arch. Pharm. Res. 35, 867–876 (2012). https://doi.org/10.1007/s12272-012-0512-1

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  • DOI: https://doi.org/10.1007/s12272-012-0512-1

Key words

  • Snake venom toxin
  • NF-κB
  • STAT3
  • Ovarian cancer cells