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Mol. Cells 2010; 29(2): 209-215

Published online February 28, 2010

https://doi.org/10.1007/s10059-010-0052-9

© The Korean Society for Molecular and Cellular Biology

Melittin Suppresses PMA-Induced Tumor Cell Invasion by Inhibiting NF-κB and AP-1-Dependent MMP-9 Expression

Jung Hyun Park1, Yun-Jeong Jeong, Kwan-Kyu Park, Hyun-Ji Cho, Il-Kyung Chung2, Kwan-Sik Min3, Mihyun Kim4, Kwang-Gill Lee5, Joo-Hong Yeo5, Kwang-Kyun Park6, and Young-Chae Chang*

Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Korea, 1Department of Rehabilitation Medicine, Eulji University Hospital, Daejeon 302-799, Korea, 2Department of Biotechnology, Catholic University of Daegu, Gyeongsan 712-702, Korea, 3Animal Biotechnology, Graduate School of Bio., and Information Technology, Hankyong National University, Anseong 456-749, Korea, 4Department of Physical Therapy, Inje University, Gimhae 621-749, Korea, 5Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon 441-100, Korea, 6Department of Oral Biology, College of Dentistry, Yonsei University, Seoul 120-752, Korea

Correspondence to : *Correspondence: ycchang@cu.ac.kr

Received: December 4, 2009; Accepted: December 22, 2009

Abstract

Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of bee venom (BV) and its major peptides, melittin and apamin, on PMA-induced invasion induced by MMP-9 expression in Caki-1 renal cancer cells. BV and melittin, but not apamin, significantly suppressed PMA-induced invasion by inhibiting MMP-9 expression in Caki-1 cells. Furthermore, as evidenced by MMP-9 promoter assays, melittin inhibited MMP-9 gene expression by blocking the PMA-stimulated activations of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB). In addition, melittin suppressed the PMA-induced phosphorylations of ERK and JNK mitogen-activated protein kinases, upstream factors involved in Ap-1 and NF-κB. These results suggest that the suppression of MMP-9 expression contributes to the anti-tumor properties of melittin.

Keywords bee venom, Caki-1 renal carcinoma cells, invasion, melittin, MMP-9

Article

Communication

Mol. Cells 2010; 29(2): 209-215

Published online February 28, 2010 https://doi.org/10.1007/s10059-010-0052-9

Copyright © The Korean Society for Molecular and Cellular Biology.

Melittin Suppresses PMA-Induced Tumor Cell Invasion by Inhibiting NF-κB and AP-1-Dependent MMP-9 Expression

Jung Hyun Park1, Yun-Jeong Jeong, Kwan-Kyu Park, Hyun-Ji Cho, Il-Kyung Chung2, Kwan-Sik Min3, Mihyun Kim4, Kwang-Gill Lee5, Joo-Hong Yeo5, Kwang-Kyun Park6, and Young-Chae Chang*

Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Korea, 1Department of Rehabilitation Medicine, Eulji University Hospital, Daejeon 302-799, Korea, 2Department of Biotechnology, Catholic University of Daegu, Gyeongsan 712-702, Korea, 3Animal Biotechnology, Graduate School of Bio., and Information Technology, Hankyong National University, Anseong 456-749, Korea, 4Department of Physical Therapy, Inje University, Gimhae 621-749, Korea, 5Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon 441-100, Korea, 6Department of Oral Biology, College of Dentistry, Yonsei University, Seoul 120-752, Korea

Correspondence to:*Correspondence: ycchang@cu.ac.kr

Received: December 4, 2009; Accepted: December 22, 2009

Abstract

Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of bee venom (BV) and its major peptides, melittin and apamin, on PMA-induced invasion induced by MMP-9 expression in Caki-1 renal cancer cells. BV and melittin, but not apamin, significantly suppressed PMA-induced invasion by inhibiting MMP-9 expression in Caki-1 cells. Furthermore, as evidenced by MMP-9 promoter assays, melittin inhibited MMP-9 gene expression by blocking the PMA-stimulated activations of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB). In addition, melittin suppressed the PMA-induced phosphorylations of ERK and JNK mitogen-activated protein kinases, upstream factors involved in Ap-1 and NF-κB. These results suggest that the suppression of MMP-9 expression contributes to the anti-tumor properties of melittin.

Keywords: bee venom, Caki-1 renal carcinoma cells, invasion, melittin, MMP-9

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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