Table 1.
Summary of representative sweeteners/their metabolites and their underlying effects on cancer.
| Sweetener Type | Targeted Metabolites/Proteins/Genes/Pathway | Targeted Disease/Tissue | Mechanism of Action | Methods of Testing | Model Used | References | |
|---|---|---|---|---|---|---|---|
| In Vivo | In Vitro | ||||||
| Steviol glycosides | Apoptosis Cellular proliferation |
Gastric cancer Colon cancer |
- It inhibited mitochondrial apoptotic pathway - Activated p21 and p53 - It increased Bax/Bcl-2 ratio |
MTT assay Western blot miRNA analysis Flow cytometry |
- HGC-27 cells - Caco-2 cells - HCT-8 cells - HCT 116 cells - MKN-45 cells - MGC-803 cells |
[67] | |
| Cytotoxic Apoptosis |
Stomach cancer | - Induced apoptosis cell death - Increased cytotoxicity |
MTT assay Apoptotic assays Flow cytometry |
- AZ521 cells | [70] | ||
| Apoptosis | Colon cancer | - It decreased cell viability in colorectal cancer cell line | MTT assay Bicinchoninic acid assay |
- Wistar rats | - Caco-2 cells | [69] | |
| Neohesperidin dihydrochalcone |
Apoptosis Angiogenesis |
Colon cancer | - It induced apoptosis and blocked angiogenesis - It altered the gut microbiota |
PCR Western blot Luciferase assay Cell survival assay TUNEL assay |
- C57BL/6 J - APCmin/+ mice |
- HCT116 cells - SW480 cells - CT26 cells |
[78] |
| Glycyrrhizin | Apoptosis | Colon cancer | - Inhibited cellular growth in a dose-dependent manner - It also induced apoptosis through nuclear fragmentation and chromatin condensation |
Transmission electron microscopy Apoptotic assay Cell invasion assay Western blot |
- SW48 cells | [72] | |
| Apoptosis Inflammation |
Colon cancer | - Treatment with glycyrrhizic acid suppressed the development of early markers of colon cancer - It also suppressed the development of precancerous lesions - Suppressed the immunostaining of NF-Kb and p65 |
Immunohistochemical staining ELISA Aberrant Crypt Foci (ACF) assay |
- Albino rats | [75] | ||
| Inflammation | Colon cancer | - It reduced the plasma level of IL-6 and TNF-a - It significantly reduced the expression of 8- NitroG, 8-OxodG, COX-2, and HMGB1 |
ELISA Immunohistochemical staining |
- ICR mice | [95] | ||
| Apoptosis Inflammation |
Colon cancer | - Treatment with glycyrrhizic acid reduced the expression of NF-kB and COX-2 - It enhanced the expression of cleaved caspase 3 - It also reduced the infiltration of mast cells |
ELISA Immunohistochemical staining Mast cell staining |
- Albino rats | [76] | ||
| Apoptosis Cellular proliferation |
Gastric cancer | - Treatment with glycyrrhizic acid downregulated the level of G1 phase-related proteins in a dose- and time-dependent manner - It also upregulated the levels of Bax; cleaved PARP; and pro-caspase-3, -8, -9 |
CCK-8 assay Apoptotic assay EdU assay Cell cycle assay Western blot |
- MGC-803 cells - BGC-823 cells - SGC-7901 cells |
[77] | ||
| Saccharin | Apoptosis Cell viability |
Intestinal epithelium | - At a lower concentration (up to 100 uM), it induced apoptosis, while at a higher concentration (<=1000 uM), it induced cell death - Decreased cell viability and disrupted the intestinal epithelial barrier through binding to the sweet taste receptors |
RT-PCR Annexin V assay siRNA and cDNA Transfections ROS assay ELISA |
- C57BL/6 mice | - Caco-2 cells | [93] |
| Sucralose | Inflammation | Colitis-associated colorectal cancer | - Significantly increased the number and size of colorectal tumors - Increased expression of TNFa and TLR4 - Increased the abundance of Firmicures, Clostridium symbiosum, and Peptostreptococcus anaerobius while decreasing the abundance of Solobacterium moorei and Bifidobacteria |
Spectrophotometry qRT-PCR Western blot ELISA |
- C57BL/6 mice | [94] | |