2. Academic Validation
  3. A Novel Naphthyridine Derivative, 3u, Induces Necroptosis at Low Concentrations and Apoptosis at High Concentrations in Human Melanoma A375 Cells

A Novel Naphthyridine Derivative, 3u, Induces Necroptosis at Low Concentrations and Apoptosis at High Concentrations in Human Melanoma A375 Cells

  • Int J Mol Sci. 2018 Sep 29;19(10):2975. doi: 10.3390/ijms19102975.
Qinghong Kong 1 2,  Jianxin Lv 3,  Shengjiao Yan 4,  Kwen-Jen Chang 5,  Guanlin Wang 6
Affiliations

Affiliations

  • 1 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China. [email protected].
  • 2 Faculty of Enviromental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China. [email protected].
  • 3 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China. [email protected].
  • 4 School of Chemical Science and Technology, Yunnan University, Kunming 650091, China. [email protected].
  • 5 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China. [email protected].
  • 6 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China. [email protected].
PMID: 30274263 DOI: 10.3390/ijms19102975
Abstract

Naphthyridine derivatives are a widely-used class of heterocycles due to their pharmacological activities. A novel compound (10-Methoxy-1,2,3,4-tetrahydrobenzo(g)(1,3) diazepino(1,2-a)-(1,8)naphthyridin-6-yl)(phenyl) methanone (named 3u), showed good Anticancer activity in the human malignant melanoma cell line A375 via Thiazolyl Blue Tetrazolium Bromide (MTT) assay. After Western blotting confirmed, we found that 3u induces Necroptosis at low concentrations and Apoptosis at high concentrations via the upregulation of death receptors and scaffold protein in A375 cells. Furthermore, by combining 3u with the Caspase Inhibitor zVAD-fmk or Receptor Interacting Serine/Threonine Kinase 1 (RIP1) kinase inhibitor Necrostatin-1 (Nec-1), we found that the activity of Caspase-8 was the crucial factor that determined whether either Apoptosis or Necroptosis occurred. The results indicate that 3u should be considered as a potential chemical substance for melanoma treatment.

Keywords

apoptosis; caspase-8; death receptors; melanoma; naphthyridine derivative; necroptosis.

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