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. 2023 Aug;53(4):883-893.
doi: 10.55730/1300-0144.5652. Epub 2023 Aug 18.

The role of curcumin on apoptosis and NLRP3 inflammasome-dependent pyroptosis on colorectal cancer in vitro

Zeynep Dal  1 , Başak Aru  2
Affiliations

The role of curcumin on apoptosis and NLRP3 inflammasome-dependent pyroptosis on colorectal cancer in vitro

Zeynep Dal et al. Turk J Med Sci. 2023 Aug.

Abstract

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. Many factors such as stress, lifestyle, and dietary habits are known to play a role in the initiation and progression of the disease. Herbal therapeutic agents including curcumin can hold a great potential against cancer treatment; however, their efficacy on CRC is still under investigation. Herein, we evaluated the anticancer mechanism of curcumin on four different CRC cell lines.

Methods: Cells were treated with curcumin for 24, 48 and 72 h, and IC50 doses for each cell line were calculated. Mechanistic studies were conducted with the lowest IC50 dose determined for each cell line by evaluating apoptosis and necrosis, cell division, and NLRP3-mediated pyroptosis.

Results: Curcumin treatment significantly decreased viability while increasing the SubG1 phase in all cell lines tested, indicating apoptosis is the main programmed cell death pathway activated upon curcumin treatment in CRC. In terms of pyroptosis, components of NLRP3 inflammasome were found to be elevated in SW480 and HCT116 cell lines, although to a lesser extent in the latter, and NLRP3 inflammasome activation was not observed in LoVo and HT29 cells.

Discussion: Our results reveal that while curcumin effectively induces apoptosis, its effects on NLRP3-inflammasome mediated pyroptosis vary. Our results underline the need for further research focusing on the other inflammasome complexes to confirm the differential effects of curcumin on CRC.

Keywords: Colorectal cancer; DNA content analysis; NLRP3 inflammasome; apoptosis; pyroptosis.

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Figures

Figure 1
Figure 1
Curcumin decreases viability significantly in the CRC cell lines while inducing apoptosis and necrosis. Bar graphics indicating (a) viability, (b) early apoptosis, (c) late apoptosis and (d) necrosis. * indicates differences between respective control and test groups; # indicates differences between treatment groups. (e) Representative flow cytometry plots. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; #p < 0.05, ##p < 0.01, ###p < 0.001, ####p < 0.0001.
Figure 2
Figure 2
Curcumin increases SubG1 phase in all cell lines and promotes cell cycle arrest in a cell line-dependent manner. Bar graphics indicate cell cycle distribution for (a) HCT116, (b) SW480, (c) LoVo, and (d) HT29. * indicates differences between respective control and test groups. (e) Representative flow cytometry histogram plots. **p < 0.01, ***p < 0.001, ****p < 0.0001.
Figure 3
Figure 3
Curcumin induces NLRP3 inflammasome complex in a cell line-dependent manner. Bar graphics indicate relative gene expression levels in terms of NLRP3 inflammasome components in (a) HCT116, (b) SW480, (c) LoVo, and (d) HT29 cell lines. * indicates differences between respective control and test groups. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
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Grants and funding

This study was supported in part by The Scientific and Technological Research Council of Türkiye (TÜBİTAK) 2209-A Research Funding for University Students in 2020.
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