Journal of Cancer Prevention

eISSN 2288-3657
pISSN 2288-3649

A summary of cancer prevention effects of beetroot in in vitro or in vivo models

No Test items and dose Experimental model Dose and treatment duration Cancer preventive effects References
In vitro antioxidant and anti-inflammatory activities
1 Beetroot ethanol extract (lyophilized)

Cell-free system using DPPH

NO inhibitory efficacy in mouse macrophage RAW 264.7 cell line

25-100 µg/mL

Good antioxidant, electron-donating ability and radical scavenging activity

Increases inhibition rate of NO production in LPS-treated cells

[55]
2 Water extracts of beetroot

Cell-free system using standard chemical tests

Cellular antioxidant activity assay in HT29 (human colon adenocarcinoma) cells

Activity of phase II detoxification enzymes: glutathione S-transferases (GST) and quinone oxidoreductase (NQO1)

10% (v/v) extracts (24 h)

10% (v/v) (6-24 h)

Strongest antioxidant potential as compared with other plants

No significant cytotoxic nor any protective effect against oxidative DNA damage in ROS challenged cells

No significant ability to induce activity of phase II detoxification enzymes

[16]
3 Betanin (red beet extract diluted with dextrin; CAS-Nr.: 7659-95-2)

Comet assay in HT-29 cells

Nrf2 dual luciferase reporter gene assay in Huh7 cells

Antioxidant enzyme heme oxygenase-1 (HO-1) expression in Huh7 cells

Glutathione (GSH) concentration in Huh7 cells

15 µM betanin (14 h)

1-15 µM betanin (24 h)

25 µM betanin (24 h)

1-15 µM betanin (24 h)

Prevents DNA damage

Induces Nrf2 at 15 µM betanin

Increases in HO-1 protein concentration

Increases cellular GSH

[56]
4 Betanin (ABCR GmbH & Co. KG, Karlsruhe, Germany)

In vitro PMA-induced DNA damage in isolated human neutrophils (PMNs)

DNA damage (Comet assay) in isolated human neutrophils

Fluorometric analysis of caspase-3 activity

200 µM betanin (30 min)

20-200 µM (24 h)

20-300 µM (24 h)

Diminishes intracellular ROS level elevated by PMA stimulation (~3 fold)

Decreases the percentage of DNA in the comet tails of the stimulated neutrophils

Enhances caspase-3 activity in stimulated neutrophils

[57]
5 Betanin (ABCR GmbH & Co. KG)

In vitro H2O2-induced DNA damage in isolated human neutrophils and Caco-2 intestinal cells

Caspase-3 activity

200 µM (24 h)

200 µM (24 h; neutrophils)

20-200 µM (24 h; Caco-2 cells)

Betanin reduces DNA damage (~14%) caused by H2O2

Enhances caspase-3 activity in neutrophils and Caco-2 cells

Triggers apoptotic cell death

[58]
In vivo antioxidant and anti-inflammatory activities
6 Beetroot juice (79.3 mg/100 mL betaxanthins and 159.6 mg/100 mL betacyanins)

NDEA and CCl4-induced oxidative stress rat model

8 mL/kg/day for 28 days

Reduces DNA damage in blood leukocytes

Restores the activity of some of the antioxidant enzymes in the liver

Prevents xenobiotic-induced oxidative stress

[59]
7 Beetroot juice (79.3 mg/100 mL betaxanthins and 159.6 mg/100 mL betacyanins

Phase I and phase II enzymes, DNA damage and NDEA-induced liver injury model in rats

8 mL/kg/day for 28 days

Reduces biomarker levels of liver injury such as ALT, SDH, GGT and bilirubin

Reduces DNA damage triggered by NDEA treatment

[60]
8 Beetroot ethanol extract (lyophilized)

Alcohol induced liver damage model in rats

200 or 400 mg/kg for 4 weeks

Decreases serum AST, ALT and γ-GTP concentrations

Decreases fat accumulation and inflammatory cell infiltration

Improves morphological characteristics of damaged liver lesion

Exert protective effects in hepatotoxicity

[55]
9 Beetroot ethanol extract (evaporated dry)

Gentamicin-induced nephrotoxicity in rats

Oxidative/nitrosative stress, inflammatory and apoptotic markers

250 and 500 mg/kg weight for 20 days before gentamicin treatment and there after concurrently with gentamicin for 8 days

Inhibits gentamicin-induced up-regulation of inflammatory markers and nitric oxide level

Reduces the expression of apoptotic markers in the kidney cells.

Reduces inflammatory infiltration in the kidney tubules

[2]
In vitro antiproliferative and other chemopreventive activities
10 Betanin and betaine isolated from beetroot extracts

MTT assay in HepG2 cells

0-200 µg/mL

800 µg/mL

Inhibits cell proliferation in a dose dependent manner

Inhibits HepG2 cells by 25%

[67]
11 Betacyanins purified from beetroot

Sulforhodamine B (SRB), apoptosis marker assay in urinary bladder cancer cells (T24) and normal human skin keratinocytes (NCTC 2544)

50 µg/mL at 24, 48 and 72 h

Betacyanins and vitexin-2-O-xyloside synergistically inhibit proliferation of tumor cells and not normal cells

Induces apoptosis markers in tumor cells

[68]
12 Beetroot extract (diluted with dextrin)

Trypan blue cell viability assay in human pancreatic (PaCa), breast (MCF-7) and prostate cancer (PC-3) cell lines

0.29-290 µg/mL at 72 h

Synergistic antiproliferative effects when used in combination with doxorubicin

IC50 values reduced to almost 40%

[69]
13 Betanin/isobetanin enriched powder from beetroot

Cell proliferation, apoptosis and autophagy assay in mouse melanoma cell line (B16F10), human breast cancer lines (MCF-7, MDA-MB-231), human colorectal cells (HT-29) and normal human fibroblasts (MRC-5)

48 h

IC50 about 25 µM for B16F10 and MCF-7 cells and 35 µM for MDA-MB-231 cells

Decreases cancer cell proliferation and viability.

Increases the expression of apoptosis-related proteins and autophagosome vesicles

[70]
14 Betavulgarin isolated from beetroot

Breast cancer cells (MDA-MB-231 and MCF-7)

MDA-MB-231 (≥ 100 µM) and MCF-7 cells at ≥ 50 µM for 24 h

Suppresses proliferation, migration, colony formation, and mammosphere formation

Reduces the size of the CD44+/CD24 subpopulation

Reduces the expression of the self-renewal-related genes, c-Myc, Nanog and Oct4

Inhibits the Stat3/Sox2 signaling pathway and induces breast cancer stem cells death

[71]
In vivo antiproliferative and other chemopreventive activities
15 E162-water (78 µg/mL E162 dye powder in water)

N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus (F344 rats)

35 weeks

Reduces NMBA-induced esophageal papillomas by 45%

Reduces rates of cell proliferation in cancerous lesions

Reduces level of angiogenesis and inflammation

Increases rate of apoptosis

[72]
16 Beetroot extract (betanin) (TCI America, Portland, OR, USA)

Mouse skin and lung carcinogenesis model

0.0025% (w/v) betanin in drinking water for 20 weeks

Inhibits TPA-induced promotion of mice skin tumors

Reduces 60% of lung tumors

[73]
17 Betanin extract (betanin) (TCI America)

VC and B(a)P-induced lung tumors in mice

25 and 100 µg/mL betanin in drinking water for 20 weeks

Decreases tumor multiplicity and tumor load

Induces caspase-3 expression

Inhibits angiogenesis

[74]
18 Beetroot extract (extracted with 70% ethanol)

γ-ray irradiation in C57BL/6 mice

400 mg/mouse orally three times

Stimulates cell proliferation

Minimizes DNA damage of splenocytes

Repopulates S-phase cells

Boosts differentiation of HSCs into burst-forming units

Enhances level of hematocrit and hemoglobin and RBC

[76]
Chemoprevention clinical studies
19 Beetroot-carrot juice

Case report of a patient diagnosed with B-cell chronic lymphocytic leukemia (B-CLL)

330 mL of fresh raw beetroot- carrot juice orally (beetroot 200 g + carrots 250 g) 2 h before breakfast 6 times/week for 1.5 month

330 mL of fresh beetroot-carrot juice 6 times per week, in combination with the chlorambucil protocol 8 mg/day for 37 days

Decreases leukocyte and lymphocyte count from

Reduces level of uric acid in blood

Increases appetite,

Improves fatigue

Decreases leukocyte, lymphocyte and reticulocyte counts

Improves renal function

Improved blood urea, serum creatinine and uric acid levels

Decreases LDH level

[77]
20 Beetroot (concentrated organic beetroot crystals)

Untreated squamous cell cancer of the head and neck (Randomized phase II Trial)

10 g Beetroot powder mixed with 4-8 oz

12 weeks

Duration of study from December 2014-May 2018

Unpublished

ClinicalTrials.gov Identifier: NCT02058849
21 Dietary supplement: beetroot juice

Malignant breast tissue neoplasm

5-day dietary nitrate intervention programme, taking 3 doses of 7 cl (centiliter) (0.4 g nitrate per dose) concentrated beetroot juice

Duration of study from May 2019-June 2020

Unpublished

ClinicalTrials.gov Identifier: NCT03944226

NO, nitric oxide; LPS, lipopolysaccharide; ROS, reactive oxygen species; NDEA, N-nitrosodiethylamine; ALT, alanine aminotransferase; SDH, sorbitol dehydrogenase; GGT, gamma glutamyl transferase; AST, aspartate aminotransferase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; VC, vinyl carbamate; B(a)P, benzo(a)pyrene; RBC, red blood cell.

J Cancer Prev 2021;26:1~17 https://doi.org/10.15430/JCP.2021.26.1.1
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