Original Research ARTICLE
Induction apoptosis of erinacine A in human colorectal cancer cells involving the expression of TNFR, Fas and Fas ligand via the JNK/p300/p50 signaling pathway with histone acetylation
- 1Department of Nursing, Chang Gung University of Science and Technology, Taiwan
- 2Kaohsiung Chang Gung Memorial Hospital, Taiwan
- 3Chiayi Chang Gung Memorial Hospital, Taiwan
- 4Grape King (Taiwan), Taiwan
Erinacine A, which is the major one of the bioactive diterpenoid compounds extracted from cultured mycelia of H. erinaceus, displays great anti-tumorigenic activity. However, the molecular mechanisms underlying erinacine A inducing cancer cell apoptosis in CRC remain unclear. This study shows that treatment with erinacine A not only triggers the activation of extrinsic apoptosis pathways (TNFR, Fas, Fas-L and caspases), but also suppresses the expression of anti-apoptotic molecules Bcl-2 and Bcl-XL via a time-dependent manner in DLD-1 cells. Furthermore, phosphorylation of Jun N-terminus kinase (JNK1/2), NFκB p50, p300 is involved in erinacine A-induced cancer cell apoptosis. Inhibition of these three signaling pathways by SP600125 (an inhibitor for JNK1/2), C646 (an inhibitor for p300), or PDTI (an inhibitor for NFκB) blocks erinacine A–induced transcriptional activation implicates histone H3K9K14ac (Acetyl Lys9/Lys14) of the TNFR, Fas, and Fas-L as promoters. Moreover, histochemical and immunohistochemical analyses revealed that erinacine A treatment significantly induced the TNFR, Fas, and Fas-L levels in the in vivo xenograft mouse model. Together, these results demonstrated an increase in the cellular transcriptional levels of TNFR, Fas, and Fas-L by erinacine A induction to cell apoptosis via the activation of the JNK, p300, and NFκB p50 signaling modules thereby providing a new mechanism for erinacine A treatment in vitro and in vivo.
Keywords: H. erinaceus, Erinacine A, Colorectal Cancer cells, Apoptosis, Death Receptors, JNK1/2, H3K9K14ac
Received: 20 May 2019;
Accepted: 12 Sep 2019.
Copyright: © 2019 Kuo, Lee, Lee, Shen, Huang, Lee, Chen, Chen, Teng, Tung and Hsieh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mx. Hsing Chun Kuo, Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan, firstname.lastname@example.org