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

Yuru Zhou; Yunyuan Kong; Mei Jiang; Linju Kuang; Jinhua Wan; Shuyuan Liu; Qian Zhang; Kuai Yu; Na Li; Aiping Le; Zhanglin Zhang

doi:10.1080/15384047.2022.2058862

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.

Authors

Yuru Zhou^{1

2}, Yunyuan Kong³, Mei Jiang⁴, Linju Kuang¹, Jinhua Wan⁴, Shuyuan Liu⁴, Qian Zhang^{1

2}, Kuai Yu^{1

2}, Na Li⁵, Aiping Le^{1

2}, Zhanglin Zhang^{1

2}

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CARD Signaling Adaptor Proteins / metabolism
Calcium-Binding Proteins
Curcumin* / pharmacology
DNA-Binding Proteins / metabolism
Humans
Inflammasomes / metabolism
Leukemia, Myeloid, Acute* / drug therapy
Leukemia, Myeloid, Acute* / genetics
NLR Family, Pyrin Domain-Containing 3 Protein / genetics
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Phosphoproteins / metabolism
Pyroptosis / genetics
U937 Cells

Substances

AIM2 protein, human
CARD Signaling Adaptor Proteins
Calcium-Binding Proteins
DNA-Binding Proteins
Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
NLRC4 protein, human
Nuclear Proteins
Phosphoproteins
IFI16 protein, human
Curcumin

Grants and funding

This work was supported by the Natural Science Foundation of China (82160037, 82160692, 32100729, 32071223), Apply Research Cultivation Program of Jiangxi Provincial Department of Science and Technology (20181BBG78072), Traditional Chinese Medicine Scientific and Technological Project of Jiangxi Provincial Health and Family Planning Commission (2017A268).