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Am J Chin Med. 2016;44(8):1719-1735. Epub 2016 Nov 16.

Allergen-Removed Rhus verniciflua Extract Induces Ovarian Cancer Cell Death via JNK Activation.

Author information

1
* Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
2
† Department of Physiology, Korea University College of Medicine, Seoul 02841, Republic of Korea.
3
‡ Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Korea.
4
§ East-West Cancer Center, Daejeon University, Daejeon 302-120, Republic of Korea.
5
¶ Department of Sasang Constitutional Medicine, College of Korean Medicine, Woosuk University, Wanju, Jeonbuk, 55338, Republic of Korea.
6
∥ Department of Molecular Medicine, College of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
7
** Department of Integrative Cancer Center, Woosuk Korean Medicine Hospital, Woosuk University, Jeonju 560-833, Republic of Korea.

Abstract

Nuclear factor-[Formula: see text]B (NF-[Formula: see text]B)/Rel transcription factors are best known for their central roles in promoting cell survival in cancer. NF-[Formula: see text]B antagonizes tumor necrosis factor (TNF)-[Formula: see text]-induced apoptosis through a process involving attenuation of the c-Jun-N-terminal kinase (JNK). However, the role of JNK activation in apoptosis induced by negative regulation of NF-[Formula: see text]B is not completely understood. We found that allergen-removed Rhus verniciflua Stokes (aRVS) extract-mediated NF-[Formula: see text]B inhibition induces apoptosis in SKOV-3 ovarian cancer cells via the serial activation of caspases and SKOV-3 cells are most specifically suppressed by aRVS. Here, we show that in addition to activating caspases, aRVS extract negatively modulates the TNF-[Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B pathway to promote JNK activation, which results in apoptosis. When the cytokine TNF-[Formula: see text] binds to the TNF receptor, I[Formula: see text]B dissociates from NF-[Formula: see text]B. As a result, the active NF-[Formula: see text]B translocates to the nucleus. aRVS extract (0.5[Formula: see text]mg/ml) clearly prevented NF-[Formula: see text]B from mobilizing to the nucleus, resulting in the upregulation of JNK phosphorylation. This subsequently increased Bax activation, leading to marked aRVS-induced apoptosis, whereas the JNK inhibitor SP600125 in aRVS extract treated SKOV-3 cells strongly inhibited Bax. Bax subfamily proteins induced apoptosis through caspase-3. Thus, these results indicate that aRVS extract contains components that inhibit NF-[Formula: see text]B signaling to upregulate JNK activation in ovarian cancer cells and support the potential of aRVS as a therapeutic agent for ovarian cancer.

KEYWORDS:

Allergen-Removed Rhus verniciflua Extract; Apoptosis; JNK; NF-B; SKOV-3

PMID:
27848251
DOI:
10.1142/S0192415X16500968
[Indexed for MEDLINE]

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