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Title: Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

Abstract

We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarianmore » cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. -- Highlights: ► Some studies have showed that bee venom and/or melittin have anti-cancer effects. ► We found that bee venom and melittin inhibited cell growth in ovarian cancer cells. ► Bee venom and melittin induce apoptosis in SKOV3 and PA-1.« less

Authors:
; ;  [1]; ;  [2];  [1];  [3]
  1. College of Pharmacy and Medical Research Center, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763 (Korea, Republic of)
  2. College of Oriental Medicine, Kyungwon University, San 65, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii 461-701 (Korea, Republic of)
  3. Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22215200
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 258; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; DEATH; INHIBITION; NEOPLASMS; PHOSPHORYLATION; RECEPTORS; RNA; TOXINS; VENOMS

Citation Formats

Jo, Miran, Park, Mi Hee, Kollipara, Pushpa Saranya, An, Byeong Jun, Song, Ho Sueb, Han, Sang Bae, Kim, Jang Heub, Song, Min Jong, E-mail: bitsugar@catholic.ac.kr, and Hong, Jin Tae, E-mail: jinthong@chungbuk.ac.kr. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2011.10.009.
Jo, Miran, Park, Mi Hee, Kollipara, Pushpa Saranya, An, Byeong Jun, Song, Ho Sueb, Han, Sang Bae, Kim, Jang Heub, Song, Min Jong, E-mail: bitsugar@catholic.ac.kr, & Hong, Jin Tae, E-mail: jinthong@chungbuk.ac.kr. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. United States. https://doi.org/10.1016/J.TAAP.2011.10.009
Jo, Miran, Park, Mi Hee, Kollipara, Pushpa Saranya, An, Byeong Jun, Song, Ho Sueb, Han, Sang Bae, Kim, Jang Heub, Song, Min Jong, E-mail: bitsugar@catholic.ac.kr, and Hong, Jin Tae, E-mail: jinthong@chungbuk.ac.kr. 2012. "Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway". United States. https://doi.org/10.1016/J.TAAP.2011.10.009.
@article{osti_22215200,
title = {Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway},
author = {Jo, Miran and Park, Mi Hee and Kollipara, Pushpa Saranya and An, Byeong Jun and Song, Ho Sueb and Han, Sang Bae and Kim, Jang Heub and Song, Min Jong, E-mail: bitsugar@catholic.ac.kr and Hong, Jin Tae, E-mail: jinthong@chungbuk.ac.kr},
abstractNote = {We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. -- Highlights: ► Some studies have showed that bee venom and/or melittin have anti-cancer effects. ► We found that bee venom and melittin inhibited cell growth in ovarian cancer cells. ► Bee venom and melittin induce apoptosis in SKOV3 and PA-1.},
doi = {10.1016/J.TAAP.2011.10.009},
url = {https://www.osti.gov/biblio/22215200}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 258,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2012},
month = {Sun Jan 01 00:00:00 EST 2012}
}