2. Academic Validation
  3. Enhancement of NK cell-mediated lysis of non-small lung cancer cells by nPKC activator, ingenol 3,20 dibenzoate

Enhancement of NK cell-mediated lysis of non-small lung cancer cells by nPKC activator, ingenol 3,20 dibenzoate

  • Mol Immunol. 2017 Mar;83:23-32. doi: 10.1016/j.molimm.2017.01.012.
Chenyuan Gong 1,  Chao Yao 1,  Zihang Xu 1,  Zhongya Ni 1,  Xiaowen Zhu 1,  Lixin Wang 2,  Xuewei Yan 1,  Wuxiong Zhou 3,  Shiguo Zhu 4
Affiliations

Affiliations

  • 1 Laboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Rd., Shanghai 201203, PR China.
  • 2 Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Rd. Shanghai 201203, PR China.
  • 3 Department of Histology and Embryology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Rd. Shanghai 201203, PR China.
  • 4 Laboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Rd., Shanghai 201203, PR China; Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Rd. Shanghai 201203, PR China. Electronic address: zhushiguo@shutcm.edu.cn.
PMID: 28092804 DOI: 10.1016/j.molimm.2017.01.012
Abstract

The IFN-γ production is crucial for NK cell-mediated lysis of Cancer cells. Thus increasing the IFN-γ production by NK cells may be an ideal strategy to improve their tumoricidal effect. Since the focus on new drug development has shifted towards Natural Products, limited information is out there about Natural Products that enhance the IFN-γ production by NK cells. In this study, through a high-throughput screening, we have identified a natural product ingenol 3,20 dibenzoate (IDB), an activator of tumor suppressor protein kinase C (PKC) isozymes, could increase the IFN-γ production and degranulation by NK cells, especially when NK cells were stimulated by non-small lung Cancer (NSCLC) cells. IDB also significantly enhanced the NK cell-mediated lysis of NSCLC cells. Furthermore, PKC Inhibitor, sotrastaurin abrogated IDB-induced IFN-γ production, degranulation and cytotoxicity, but did not affect IFN-γ production by NK cells without IDB treatment and NSCLC cell stimulation. The IFN-γ neutralization reversed the IDB-induced enhancement of NK cell mediated killing. In conclusion, our study indicated that IDB enhanced NK cell-mediated lysis of NSCLC cells is dependent on specific PKC mediated IFN-γ production and degranulation. Thus, IDB may have a promising application in clinic for NK cell-based Cancer Immunotherapy.

Keywords

Antitumor; IFN-γ; Ingenol 3,20 dibenzoate; NK cells; PKC activator.

Figures
Products