Betacyanins and their anticancer properties.
| Source | Model: in vitro | Dosage/Duration of treatment | Biological effects and mechanisms of action | References |
|---|---|---|---|---|
| Beta vulgaris L. (red beetroot) | Human breast (MCF-7) | Proliferative index (ratio between viable cell counts 48 h post-seeding and number of seeded cells) was used to estimate the cell viability after treatment of betanin/isobetanin concentrate. Cells were treated using concentrations from 10, 20, 30, 40 µM and were incubated for 24 h to 48 h. | Extrinsic and intrinsic apoptotic pathways—morphological changes and DNA fragmentation observed; ↑ expression levels of apoptosis-related proteins such as Bad, TRAILR4, FAS, phosphorylated p53; ↓ mitochondrial membrane potential; lower percentage of cells arrested at G1 phase (for 2D culture), higher percentage of cells in the S phase (for 3D culture); ↑ autophagic activity. | Nowacki et al. [176], 2015 |
| Human bladder (T24) | Sulforhodamine B (SRB) assay was used to measure cell viability. Cells were treated at different concentrations (25, 50, 100 µg/mL), and then incubated for 24, 48, and 72 h. | Extrinsic apoptotic pathway—betacyanin downregulated the pro-survival gene CTNNB1 (β-Catenin), resulting in the reduction of cell proliferation via induction of caspase-8 activity. | Scarpa et al. [177], 2016 | |
| Human colon (Caco-2) | MTT assay was used to evaluate the cytotoxicity of betanin, cells were treated with various concentrations (100, 200, 300, 400, 500 µM) and incubated for 24 h at 37°C. | Intrinsic apoptotic pathway—betanin ↑ DNA damage in a concentration-dependent manner and ↓ the mitochondrial transmembrane potential, as well as induced procaspase-3 cleavage and caspase-3 activity. | Zielińska-Przyjemska et al. [190], 2016 | |
| Human colon (Caco-2, HT-29) | MTT assay was used to test the beetroot hydro-alcoholic extract (BHE) at various concentrations (20, 40, 60, 80, 100, 120, 140 µg/mL) and then incubated for 24 h and 48 h. | Extrinsic and intrinsic apoptotic pathways—with the treatment of BHE, higher percentage of cells found to be undergoing early and late apoptosis stage as morphological changes (DNA fragmentation, cell shrinkage) were observed. After treated with BHE for 48 h, pro-apoptotic genes such as Bad, Fas-R, caspase-3, caspase-8, and caspase-9, were upregulated and the expression levels of anti-apoptotic gene Bcl-2 was greatly reduced. | Saber et al. [178], 2023 | |
| Human liver (HepG2) | MTT assay was used to evaluate the antiproliferative effects of betacyanin-modified selenium nanoparticles (Bc@SeNPs). Cells were treated with various concentrations (10, 20, 30, 40 µg/mL) and incubated for 24, 48, and 72 h. | Extrinsic and intrinsic apoptotic pathway—appearance of cells became round and vacuolated after treated with Bc@SeNPs. Cellular ROS levels ↑ greatly, followed by ↓ in mitochondrial membrane potential, resulting in upregulation of p53 gene, activation of caspase-3 and caspase-9 cleavage, as well as downregulation of Bcl-2 gene. | Tang et al. [182], 2021 | |
| Human liver (HepG2) | Cell Counting Kit-8 (CCK-8) was used to determine the cell viability after being treated and incubated for 24 h with red beetroot juices fermented by water kefir grains. | Apoptotic cell death—fermented beetroot juices found to have induced ROS production, ↑ both early and late apoptosis rates, and arrested cells at G1 phase, thus ↓ the number of cells entering next cell cycle. | Wang and Wang [186], 2023 | |
| Basella rubra L. (Basellaceae) | Human cervical (SiHa) | MTT assay was used to determine the cytotoxic effects of betalains. Different concentrations were used (2.5, 5, 10, 15, 20, 25, 37.5, 50, 62.5, 75, and 100 mg/mL) and then cells were incubated for 24 h. | Apoptotic cell death—morphological changes of the cells were observed after 24 h of treatment, including cell shrinkage, detachment of cells from substratum, and blebbing. | Kumar et al. [185], 2015 |
| Opuntia ficus-indica (cactus pear) | Human chronic myeloid leukemia (K562) | MTT assay was used to assess the cell proliferation and treated with betanin (10, 20, 40 and 80 µM) and then incubated for 24 h. | Extrinsic and intrinsic apoptotic pathways—DNA fragmentation and morphological changes such as blebbing and chromatin condensation were seen after treated with betanin. Higher percentage of cells were at sub G0/G1 phase, leading to ↓ number of cells that enter the S and G2 phase of cell cycle. The mitochondrial membrane potential has also been changed, hence there is an ↑ in the cytosolic levels of cytochrome c which was released by the mitochondria. Poly (ADP-ribose) polymerase (PARP) cleavage is also being induced for apoptotic cell death. | Sreekanth et al. [174], 2007 |
| Chenopodium formosanum (Djulis) | Human liver (HepG2) | MTT assay was used to test for the cell viability, various concentrations of ethanolic extracts (50, 250, 500 µg/mL) were used and the cells were incubated for 24, 48, and 72 h. | Extrinsic and intrinsic apoptotic pathways—after treatment with betanin, morphological changes such as chromatin condensation and nuclear fragmentation were seen, ↑ percentage of cells arrested in the sub-G0 phase, as well as ↑ percentage of cells in early or late apoptosis/necrosis. ROS generation was induced, and mitochondrial membrane potential was significantly ↓, resulting in upregulation of caspase-3 activity and cleavage of PARP protein. | Chu et al. [181], 2020 |
↑: increase; ↓: decrease; ROS: reactive oxygen species; Bcl-2: B-cell lymphoma 2; Bad: Bcl-2-associated agonist of cell death; TRAILR4: TNF-related apoptosis-inducing ligand receptor 4.
The authors would like to thank Mr. James Wong Yung Khai and Mr. Luther Ku for their assistance in drawing some of the diagrams in this manuscript. English grammar was improved using the Grammarly application and proofread by Dr. Elvin M. Walemba.
ODJ: Supervision, Project administration, Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing. WGS: Investigation, Visualization, Writing—original draft. APGdS: Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing. SAT: Investigation, Writing—original draft, Writing—review & editing, Validation. CYB: Investigation, Writing—original draft, Writing—review & editing, Validation. RN: Investigation, Writing—original draft, Writing—review & editing, Validation. EMW: Investigation, Writing—original draft, Writing—review & editing, Validation. ATM: Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing, Validation. All authors have read and agreed to the published version of the manuscript.
The authors declare that there are no conflicts of interest.
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