2. Academic Validation
  3. 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

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

  • Front Pharmacol. 2019 Oct 15:10:1174. doi: 10.3389/fphar.2019.01174.
Ko-Chao Lee 1 2,  Kam-Fai Lee 3,  Shui-Yi Tung 4 5,  Wen-Shih Huang 5 6,  Li-Ya Lee 7,  Wan-Ping Chen 7,  Chin-Chu Chen 7,  Chih-Chuan Teng 8 9,  Chien-Heng Shen 4 10,  Meng-Chiao Hsieh 6 10,  Hsing-Chun Kuo 8 9 11 12
Affiliations

Affiliations

  • 1 Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
  • 2 Department of Information Management & College of Liberal Education, Shu-Te University, Kaohsiung, Taiwan.
  • 3 Department of Pathology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
  • 4 Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
  • 5 School of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan.
  • 6 Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
  • 7 Grape King Bio Ltd, Taoyuan, Taiwan.
  • 8 Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.
  • 9 Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
  • 10 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 11 Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
  • 12 Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan.
PMID: 31680958 DOI: 10.3389/fphar.2019.01174
Abstract

Erinacine A, which is one of the major bioactive diterpenoid compounds extracted from cultured mycelia of H. erinaceus, displays great antitumorigenic activity. However, the molecular mechanisms underlying erinacine A inducing Cancer cell Apoptosis in colorectal Cancer (CRC) remain unclear. This study found that treatment with erinacine A not only triggers the activation of extrinsic Apoptosis pathways (TNFR, Fas, FasL, and caspases) but also suppresses the expression of antiapoptotic 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, and p300 is involved in erinacine A-induced Cancer cell Apoptosis. Inhibition of these signaling pathways by kinase inhibitors blocks erinacine A-induced transcriptional activation implicates histone H3K9K14ac (Acetyl Lys9/Lys14) of the TNFR, Fas, and FasL as promoters. Moreover, histochemical and immunohistochemical analyses revealed that erinacine A treatment significantly induced the TNFR, Fas, and FasL levels in the in vivo xenograft mouse model. Together, these results demonstrated an increase in the cellular transcriptional levels of TNFR, Fas, and FasL 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; H3K9K14ac; JNK1/2; apoptosis; colorectal cancer cells; death receptors; erinacine A.

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