1. Academic Validation
  2. Curcumin activates NLRC4, AIM2, and IFI16 inflammasomes and induces pyroptosis by up-regulated ISG3 transcript factor in acute myeloid leukemia cell lines

Curcumin activates NLRC4, AIM2, and IFI16 inflammasomes and induces pyroptosis by up-regulated ISG3 transcript factor in acute myeloid leukemia cell lines

  • Cancer Biol Ther. 2022 Dec 31;23(1):328-335. doi: 10.1080/15384047.2022.2058862.
Yuru Zhou 1 2 Yunyuan Kong 3 Mei Jiang 4 Linju Kuang 1 Jinhua Wan 4 Shuyuan Liu 4 Qian Zhang 1 2 Kuai Yu 1 2 Na Li 5 Aiping Le 1 2 Zhanglin Zhang 1 2
Affiliations

Affiliations

  • 1 Departments of Blood Transfusion, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 2 JiangXi Key Laboratory of Transfusion Medicine, Nanchang, Jiangxi, China.
  • 3 Department of Physical Examination, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 4 Departments of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 5 Departments of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Abstract

Curcumin, the primary bioactive component isolated from turmeric, has been found to possess a variety of biological functions, including anti-leukemia activity. However, the effect of curcumin in different leukemia cells vary. In this study, we demonstrated that curcumin induced the expression of AIM2, IFI16, and NLRC4 inflammasomes in leukemia cells U937 by increasing the expression levels of ISG3 transcription factor complex, which activated Caspase 1, promoted cleavage of GSDMD, and induced Pyroptosis. We also found that Pyroptosis executor GSDMD was not expressed in two curcumin-insensitive cells HL60 and K562 cells. In addition, exogenous overexpression of GSDMD by lentiviral transduction in K562 cells increased the anti-cancer activity of curcumin, and inhibiting the expression of GSDMD by shRNA enhanced U937 cells to resist curcumin. The results showed that inducing Pyroptosis is a novel mechanism underlying the anti-leukemia effects of curcumin.

Keywords

Curcumin; GSDMD; inflammasome; leukemia; pyroptosis.

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