Table 1.
Preclinical experimental evidences on the use of pectin and modified pectins in cancer.
| Cancer Type | Drug | Dose | Study Model | Outcomes | Ref. |
|---|---|---|---|---|---|
| Breast cancer |
PectaSol-C modified citrus pectin (MCP) |
MCP (0.25–1.0 mg/mL) | In vitro (human breast cancer cells) | ↓ Breast cancer cell migration and suppress adhesion of breast cancer cells | [15] |
| Pectic acid | (0, 0.1, 0.1, 0.5, 1% w/v) | In vitro (4T1 breast cancer cells) | Induce apoptosis, ↓ cell growth ↓ cell attachment, fragmented chromatin, blocked the sub-G1 phase |
[18] | |
| Pectin-mediated gold nanoparticles (p-GNPs) | (2, 4, 6, 8 and 10 µg/mL) | In vitro (human breast adenocarcinoma cell lines) | ↓ Cell viabilities ↑ Sub-G1 population |
[19] | |
| Citrus-pectin nanoemulsion | 5,10, and 65.5 μg/mL of CP/ZEO |
In vitro (human breast cell line and normal fibroblasts cell) | ↑ Reactive Oxygen Species (ROS) ↑ mitochondrial membrane potential (MMP) loss ↑ DNA damage ↑ G2 and S-phase arrest |
[17] | |
| Modified citrus pectin (MCP) | 1% (w/v) MCP | In vivo (athymic mice) | ↓ Tumor growth ↓ Angiogenesis ↓ Spontaneous metastasis |
[74] | |
| Citrus pectin or apple pectin | 1% (w/v) Cp or Ap | In vitro (human breast cell line and normal fibroblasts cell) | Suppressed the viability in MDA-MB-231, MCF-7 and T47D human Breast cancer cells, ↓ mRNA expression of galectin-3 | [16] | |
| Pectin-guar gum-zinc oxide (PEC-GG-ZnO) | (25 µg/mL to 200 µg/mL) | In vitro (breast cancer cell lines, MCF-7) | Enhancing cytotoxicity towards lung ↑ effector: target ratios from 2.5:1 to 20:1 ↑ Cancer cell death |
[20] | |
| Gastric cancer |
Low-molecular-weight citrus pectin (LCP) | (0.625 to 10.0 mg/mL) | In vitro (AGS gastric cancer cell-line) |
↓ Cell viabilities ↓ Cyclin B1 expression ↓ Galectin-3 (GAL-3) expression |
[23] |
| Pectic-oligosaccharide | (10, 20 and 30 µg/mL) | In vitro (AGS human gastric carcinoma cells) | ↓ Galectin-3 activity ↓ Growth of AGS cells Inducing apoptosis |
[75] | |
| pH-modified citrus pectin (MCP) | low-dose MCP (0.8 mg/mL) high-dose MCP (1.6 mg/mL) |
In vivo (mice) | ↓ Tumor size | [21] | |
| Colon cancer | Modified citrus pectin (MCP) | 0.0%, 0.0%, 1.0%, 2.5% and 5.0% (w/v) |
In vivo (Balb/c mice) | ↓ Liver metastases ↑ Serum galectin-3 |
[33] |
| Lyophilized pectin | 1 to 10 mg mL−1 | In vitro (Caco-2 cells) | Antiproliferative effect, ↓ Agglutination of red blood cells by galectin-3 |
[57] | |
| Apple extract | Apple extracts (0.01%, 0.02%, 0.05% and 0.1%) | In vitro (HT29, HT115, and CaCo-2 cell lines) | Protection against DNA damage, inhibit invasion | [27] | |
| Sweet potato pectin (SPP) | 0.0025 g/mL of SPP | In vitro (HT-29 cells) | ↑ Galacturonic acid (GalA), arabinose and galactose content, ↓cell proliferation, induced apoptosis | [31] | |
| Pectin | FP diets contained 3.5 g of corn oil per 100 g of diet | In vivo (Sprague–Dawley rats) | Enhanced colonocyte apoptosis suppressing of PPARd and PGE2 elevating of PGE3 |
[24] | |
| Pectin | 5%, 10% pectin | In vivo (Sprague–Dawley rats) | Suppressing colon carcinogenesis | [25] | |
| Pectin-encrusted gold nanocomposites | DMH + PA-PGNPs (PA equivalent to 2 mg/kg/day, oral) | In vivo (Albino rats of Wistar strain) | Suppression of colon carcinogenesis, dysregulating of proliferation markers | [26] | |
| High and low methoxy pectins (HP and LP) | 0.01–1.0 mg/mL | In vitro (Caco-2 cells) | Concentration-dependent effect on inhibiting of Caco-2 cells proliferation | [76] | |
| Pectin oligosaccharides | (0.1 mg/mL to 1 mg/mL) | In vitro (colon cancer HT-29 cell line | ↓ Proliferation ↑ Cytotoxicity ↓ Cell viability |
[77] | |
| Modified sugar beet pectin | 0.2, 0.5 or 1.0 mg/mL | In vitro (HT29 and DLD1 colon cancer cells) | Inducing apoptosis Cell cycle arrest Reducing proliferation |
[78] | |
| Rhamnogalacturonan I domain-rich pectin | 0 or 5 mg/mL | In vitro (colon cancer HT-29 cell line) | Inhibiting proliferation Significant G2/M cell cycle arrest. Downregulate cyclin B-1 and cyclin dependent kinase 1 expression |
[29] | |
| Pancreatic cancer | Pectin-like polysaccharide named RP02-1 | (0 µM, 4.31 µM, 8.62 µM) | In vitro (pancreatic cell line HPDE6-C7) | ↓ Cancer cell proliferation, migration and colony formation, induced pancreatic cancer cells apoptosis, suppressed autophagy | [35] |
| LRP3-S1 | (0, 4.36, 8.71 μM) | In vitro (pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1) | Attenuated invasion ability, downregulated protein expression of p-FAK, p-AKT, p-GSK-3β and p-p38 MAP kinase |
[36] | |
| Pectin | 0–1000 μg/mL | In vitro (BxPC-3 and PANC-1 cells) | Inhibit cell growth | [79] | |
| Colorectal cancer | Thiolated pectin–doxorubicin (DOX) conjugate | (Equivalent to 0.15 mg/kg DOX) | In vivo (BALB/c mice) | Inhibited the growth of all cell lines, primary tumor growth and suppressed tumor metastases | [80] |
| Apple pectin | (0.05–0.5 mg/mL with or without 5 nM SN-38) | In vitro (human colon cancer cell lines) | ↓ Viability of HCT 116 and Caco-2 inducing apoptosis, ↑ Intracellular ROS production, ↑ Cytotoxic and proapoptotic effect of irinotecan |
[81] | |
| Citrus pectin and modified citrus pectin | (20%) | In vivo (Fischer 344 rats) |
Rise to a tumorigenesis prevention, ↓ pH in caecum lumen and increase in acetate and lactic acid levels |
[82] | |
| Pectin co-functionalized dual layered solid lipid nanoparticle | Pectin solution (2%) | In vivo (zebrafish model) | Arresting G2/M phase, improving the oral bioavailability of curcumin (CMN) | [83] | |
| Heat-treated Helianthus annuus L. pectin (HT-HAP), alkali-inactivated HT-HAP | 150, 300, 110 or 220 mg/kg body weight | In vivo (female Balb/c mice) | Induced apoptosis, reduced tumor growth | [84] | |
| Pectin | 200 µmol/L pectin. | In vitro (HT-29 cells) | ↓ Expression of dynamin-related protein-1. ↑ Expression of the mitochondrial fusion-associated proteins mitofusin-1 and 2. Blockade of G2/M transition. ↑ Expression of p53 protein |
[85] | |
| Pectin | (0.25, 0.5 and 1 mg/mL) | In vitro (HT-29 cells) | Inhibited adhesion, invasion, proliferation and anchrogen-independent growth | [86] | |
| Modified apple polysaccharides | (1.0–0.01 mg/mL) | In vitro (CRC cell lines, HT-29 and SW620) | Reduced LPS-induced NF-κB expression Suppressed LPS-induced migration and invasiveness |
[87] | |
| Hepatocellular cancer | 5-FU loaded pectin-based nanoparticles (5-FU-NPs) | 0.5 to 0.006 mM for 5-FU and 5- FU-NPs | In vitro (HepG2 and A549 cells) | Exhibited size-induced prolonged circulation as well as ASGP receptor-mediated targeting ability to cancer cell lines | [40] |
| Pectin-deoxycholic acid | Citrus pectin (1.54 g) | In vitro (HepG2 cells) | ↑ Cytotoxicity, ↓ Relative migration of HepG2 cells, ↑ micelles cellular uptake | [88] | |
| Pectin-capped gold nanoparticles (PEC-AuNPs) | 100 mL of 0.03% Pectin solution | In vitro (human Caucasian hepatocyte cells) |
Greater potency in killing, proving a promising carrier for anticancer drug | [39] | |
| Bladder cancer | Modified citrus pectin (MCP) | 0.125 to 2%, (w/v) | In vitro (T24 and J82 human UBC cells) | ↓ Cell proliferation, ↓ galectin-3 Inactivation of Akt signaling pathway, ↓ tumor growth |
[45] |
| Pectin oligosaccharide (POS) | 0–30 µg/mL | In vitro (SV-HUC-1 cells) | Promoted the apoptosis of bladder cancer cells, activated the Hedgehog pathway | [46] | |
| Prostate cancer | Modified citrus pectin | 0.01–1.0% (w/v) | In vivo (Rats) | Inhibited MAT-LyLu cell adhesion | [22] |
| PectaSol-C modified citrus pectin (MCP) | 0.1%, 1.0% | In vitro (LNCaP and PC3 cells) | Inhibited MAP kinase activation, ↑ expression level of its downstream target Bim, a pro-apoptotic protein, and induced the cleavage of Caspase-3 in PC3 and CASP1, ↓ cell proliferation and apoptosis |
[47] | |
| Modified citrus pectin | 0.3% | In vitro (human prostate cancer cells) | ↑ Cisplatin-induced apoptosis of PC3 cells, ↑ calpain activation | [89] | |
| Modified citrus pectin | 25 mg/mL | In vitro (human prostate carcinoma cells) | ↓ Gal-3, cleavage of the precursor of caspase-3, ↑ expression of the pro-apoptotic protein Bax, ↓ DNA repair pathways, poly-ADP-ribose polymerase | [48] | |
| Fractionated pectin powder | (0.01–3 mg/mL) | In vitro (Prostate cancer cell lines, LNCaP and LNCaP C4-2) | Induced apoptosis | [90] | |
| Modified citrus pectin (Pectasol) | PectaSol (0.5, 1, 3 and 5 mg/mL), |
In vitro (Human PCa DU-145 and LNCaP cells) | ↑ Sub-G1 arrest, G2/M arrest ↑ p53, p27 and Bcl-2 expression Inducing cell death through apoptosis and cell growth arrest |
[49] | |
| Ovarian cancer | Modified citrus pectin (Pect-MCP) | Pect-MCP (0.025, 0.05, 0.1%) | In vitro (human ovarian cancer SKOV-3 cells) | ↑ Cell proliferation, ↓ caspase-3 activity, ↑ substrate-dependent adhesion in the presence of rhGal-3 | [50] |
| PectaSol-C modified citrus pectin (Pect-MCP) |
Pect-MCP (0.025%) | In vitro (human ovarian cancer SKOV-3 cells) | ↓ Expression of downstream target HIF-1α ↓ integrin mRNA levels ↓ AKT activity |
[54] | |
| Cervical cancer | Pectin, guar gum and zinc oxide nanocomposite |
(25, 50, 100 and 200 μg/mL) | In vitro (Cervical adenocarcinoma (HeLa) cell lines) |
Induced mitochondrial depolarization, reactive oxygen species generation, caspase-3 and Poly (ADP-ribose) polymerase 1 (PARP1) activation resulting in DNA fragmentation. | [71] |
| Leukemia | Modified citrus pectin (MCP) | (0–800 μg/mL) | In vitro (blood samples and normal lymphocytes) |
Activated T-cytotoxic cells B-cell, and NK-cells | [55] |
| Ginseng pectins | (0.1, 0.5, 2 mg/mL | In vitro (Jurkat cells (human leukemia T-cell line)) | ↓ ROS/ERK pathway, ↑ T-cell proliferation and IL-2 expression ↓ Tumor growth by 45%, ↓ Gal-3-induced T-cell apoptosis |
[56] | |
| Lyophilized pectin | 1 to 10 mg mL−1 | In vitro (THP-1 cells) | Activation of caspase-3 in THP-1 cells, triggered apoptosis | [57] | |
| Pectic oligosaccharides | (5%) | In vivo (male BALB/c mice) | ↓ Metabolic alterations ↑ Acetate in the caecal content. Counteracted the induction of markers controlling β-oxidation |
[91] | |
| Myeloma | GCS-100 | GCS-100 (0–800 µg/mL) | In vitro Myeloma cell lines U266 and RPMI 8226 |
Induced inhibition of proliferation, accumulation of cells in sub-G1 and G1 phases, and apoptosis with activation of both caspase-8, upregulating cell-cycle inhibitor p21Cip1, reduction in signal transduction |
[59] |
| Alkali-soluble pectin | 5% | In vitro (human myeloma cell line) | Suppressed IgE production | [58] | |
| GCS-100 | 350 or 700 µg/mL 220 or 500 µg/mL |
In vitro (multiple myeloma cell lines MM.1S, MM.1R, RPMI-8226, LR-5, U266, and DOX-40) | Inhibited multiple myeloma cell growth, induced apoptosis, activated caspase-8 and caspase-3 | [62] | |
| Skin cancer | pH-modified citrus pectin (MCP) | 0.5% CP or 0.5% MCP. |
In vitro | Inhibited anchorage-independent growth, Inhibited cells adhesion to laminin and asialofetuin | [65] |
| Modified citrus pectin (MCP) or citrus pectin | 0.05% CP or 0.05% MCP. |
In vitro (B16-F1 melanoma cells) | ↓ B16-F1 experimental metastasis | [64] | |
| Pectin or MCP | (1–750 µg/mL) | In vitro (HaCaT cell line) | Exhibited a stronger cytotoxic and anti-proliferative effect | [67] | |
| Brain cancer | Pectin extract (GW) | 10–400 μg mL−1 of GW | In vitro (U251-MG and T98 G human glioblastoma cell lines) | Induced cytotoxicity, ↑ cellular ROS levels | [68] |
| Modified pectin | 50μL stock 3% solution | In vitro (C6 glioma cells) | ↓ Metabolism of C6 glioma cells, ↓ Cell viability | [92] | |
| Lung cancer | Pectin-guar gum-zinc oxide (PEC-GG-ZnO) | (25 µg/mL to 200 µg/mL) | In vitro (lung cancer cell lines, A549) | Enhanced cytotoxicity towards lung ↑ effector: target ratios from 2.5:1 to 20:1, ↑ cancer cell death |
[20] |
| Pectin-modified magnetic nanoparticles (Fe3O4/Pectin/Au) | (0–1000 μg/mL) | In vitro (human lung cancer cell lines) | Lowest IC50 values | [72] | |
| Pectin, guar gum and zinc oxide nanocomposite |
(25, 50, 100 and 200 μg/mL) | In vitro (lung adenocarcinoma (A549)) | Induced mitochondrial depolarization, reactive oxygen species generation, caspase-3 and Poly (ADP-ribose) polymerase 1 (PARP1) activation resulting in DNA fragmentation | [71] | |
| Pomegranate fruit extract (PFE) | (0.1 and 0.2%, w/v) | In vitro (lung adenocarcinoma (A549)) | Inhibition of tumor growth, ↓protein expressions of cyclins D1, D2 and E ↓ cyclin-dependent kinase (cdk) 2, cdk4 and cdk6 expression. Inhibition phosphorylation of MAPK proteins, PI3K, Akt, NF-kB and IKKa, (v) degradation |
[73] | |
| Pectin-PVP based curcumin particulates | CP3 (2.5, 25 and 250 µg/mL) | In vitro (A549 cells are adenocarcinomic human alveolar basal epithelial cells) | Enhancement in anti-tumor potential | [93] |