Introduction
The polysaccharides characterizations of G. lucidum
GLPs source | Monosaccharides composition | Molecular weight | Refs. |
---|---|---|---|
Fruiting bodies | D-Glu, D-Gal, D-Man, L- (or D)-Ara, D-Xyl, and L-Fuc | 0.8 ~ 1 × 105 Da | [107] |
Spore | Backbone: D-Glu Branch: D-Glu | 1.40 × 104 Da | [6] |
Submerged culture broth of G. lucidum | Backbone: D-Gal Branch: L-Arb, D-Glu, D- Man, D-Rha | 2.2 × 104 Da | [62] |
Fruiting bodies | Backbone: D-Gal, D-Glu Branch: L-Fuc | 1.2 × 104 Da | |
Fruiting bodies | Backbone: D-Gal, D-Glu Branch: L-Fuc | 2.8 × 104 Da | |
Fruiting bodies | LZ-D-4: L-Ara, L-Fuc, D-Gal, D-Glu, D- Man, D-Xyl LZ-D-9: L-Fuc, D-Gal, D-Glu, D- Man | LZ-D-4: 1.56 × 104 Da LZ-D-4: 1.30 × 104 Da | |
Fruiting bodies | Backbone: D-Gal, D-Glu Branch: D-Glu, L-Fuc | 7 × 103 Da | |
Fruiting bodies | GLP-1: D-Glu GLP-2: D-Glu | GLP-1: 5.2 × 103 Da GLP-2: 1.54 × 104 Da | [67] |
Fruiting bodies | Backbone: D-Gal, D-Glu Branch: D-Glu, L-Fuc | 1.12 × 104 Da | [126] |
Fruiting bodies | Backbone: D-Gal, D-Glu Branch: D-Gal, D-Glu | 2.5 × 106 Da | [40] |
Spore | Backbone: D-Glu Branch: D-Glu | 1.03 × 105 Da | [20] |
Fruiting bodies | D-Glu | 3.979 × 103 Da | [50] |
Fruiting bodies | Backbone: D-Glu Branch: D-Gal | 3.75 × 106 Da | [70] |
Fruiting bodies | Backbone: D-Gal, D-Glu, D-GluA, L-Rha Branch: D-Glu | 1.002 × 105 Da | [82] |
Spore | D-Glu | 1.579 × 105 Da | [117] |
Spore | Backbone: D-Glu Branch: D-Glu | 1.5 × 104 Da | [25] |
Fruiting bodies | GLPHWE: L-Ara, D-Gal, D-Glu, D- Man, D-Rha GLPUAE: L-Ara, D-Gal, D-Glu, D- Man, D-Rha | GLPHWE: 7.03 × 105 Da GLPUAE: 4.65 × 105 Da | [48] |
Fruiting bodies | GLP: D-Fru, D-Gal, D-GalA, D-Glu, D-GluA, D- Man, D-Rha, D-Xyl Degraded GLP: D-Fru, D-Gal, D-GalA, D-Glu, D-GluA, D- Man, D-Rha, D-Xyl | GLP: 3.06 × 106 Da Degraded GLP: 1.36 × 104 Da | [123] |
Fruiting bodies | GLP-1: D-Gal, D-Glu GLP-2: D-Glu | GLP-1: 1.072 × 105 Da GLP-2: 1.95 × 104 Da | [58] |
Spore | Backbone: D-Glu Branch: D-Glu | 1.93 × 105 Da | |
Fruiting bodies | D-Gal, D-Glu, D- Man, D-Xyl, L-Fuc | 2.05 × 104 Da | [12] |
Spore | Backbone: D-Glu Branch: D-Glu | 1.28 × 105 Da | [99] |
Spore | L-Ara, D-Gal, D-Glu | 8.2 × 104 Da | [118] |
The association between structures of GLPs and their bioactivity
Tertiary structure: a key to enhanced bioactivity
Molecular weight: controversies and impacts
Degree of backbone branching: a balancing act
Monosaccharide composition: a bioactive diversity
Homopolysaccharides vs. Heteropolysaccharides: diverse anti-tumor properties
The role of specific glycosidic bonds: essential for bioactivity
Future directions: the promise of customized therapies
Anti-cancer properties of GLPs
Cancer type | GLP dose | Study model | Effects | Mechanism | References |
---|---|---|---|---|---|
Breast | In vitro: 0–0.4 μM, 0–72 h | In vitro: MCF-7 cell lines | Decreased cell viability, arrested the cell cycle at the sub-G1 phase, induced apoptosis | ↑: cytochrome C, activated caspase-3, -9, and PARP ↓: – | [95] |
In vivo: GLP: 200–400 mg/kg/day paclitaxel: 12.5 mg/kg, twice a week | In vivo: xenograft mice | Reduced tumor growth and size, restored the anti-cancer immune cells, and recovered gut microbiota dysbiosis stimulated by paclitaxel | ↑: – ↓: GLUT3, LDHA, PDK | [109] | |
In vitro: 0–160 μg/mL, 24 h In vivo: 8 mg/kg | In vitro: 4T1 cell lines In vivo: xenograft mice | Declined the number and size of 4T1 cells, increased radiosensitivity, reduced tumor growth, promoted apoptosis, and inhibited lung metastasis | ↑: INF-γ/IL-4 ratio ↓: | [132] | |
In vivo: Au-GLPs (30 mg/kg/every four days, 12 days), Dox (4 mg/kg) | In vivo: xenograft mice bearing 4T1 breast cancer tumors | Reduced tumor weight, decreased body weight loss rate, reduced pulmonary metastasis, and increased CD4 + and CD8 + T cell proliferation | ↑: – ↓: – | [137] | |
Cervical | In vivo: 0–300 mg/kg/day, 40 days | In vivo: rats bearing cervical cancer | Increased antioxidant activity and reduced inflammation | ↑: CAT, GSH-Px, and SOD ↓: IL-1β, IL-6, and TNF-α | [121] |
In vivo: GLPs (30 mg/kg/day, 14 days), cisplatin (5 mg/kg/day, 14 days) | In vivo: xenograft mice | Induced apoptosis, enhanced the spleen and thymus indexes, decreased the toxicity effects on hepatic and renal functions | ↑: Bax ↓: Bcl-2 | ||
In vivo: 0–500 μg/mL, 0–72 h | In vitro: C-33A and HeLa cell lines | Reduced cell viability, induced apoptosis, arrested the cell cycle, suppressed the development of the EMT process | ↑: Bax, cleaved caspase-3 and –9, E-cadherin, ↓: Bcl-2, N-cadherin, Slug, Vimentin, p- JAK, p-STAT5 | [46] | |
Colon and Colorectal | In vitro: 0.625–5 mg/mL, 0–72 h | In vitro: HCT-116 cell lines | Reduced cell viability suppressed cell migration, changed cell morphology | ↑: Ca2+, caspase-8, Fas ↓: - | |
In vitro: 0–10 mg/mL, 0–72 h | In vitro: HCT-116 cell lines | Reduced cell viability, arrested the cell cycle at the S phase, promoted apoptosis, and DNA fragmentation | ↑: Bax to Bcl-2 ratios, caspase-3, caspase-9, PARP ↓: | ||
In vitro: 0–10 mg/mL, 0–72 h | In vitro: LoVo cell lines | Declined cell viability, suppressed cell migration, induced apoptosis and DNA fragmentation | ↑: Caspase-3, Caspase-8, Caspase-9, Fas, PARP ↓: | [65] | |
In vitro: 200 μg/mL, 24 h | In vitro: HT29 (p53R273H) and SW480 (p53 R273H&P309S) | Promoted apoptosis, recovered p53 | ↑: Bax, p21, p53 ↓: | [44] | |
In vitro: 0–7.5 mg/mL, 0–48 h In vivo: 0–300 mg/kg/day, six weeks | In vitro: HCT116 cell lines In vivo: Xenograft mice | Reduced cell viability, inhibited the cell cycle progression, stimulated apoptosis, decreased tumor growth | ↑: caspase-3, caspase-9, NAG-1, p21 ↓: Bcl-2, cyclin A2, cyclin B1, Ki67, PCNA, survivin | [77] | |
In vivo: 393.75 g/kg/day | In vivo: xenograft mice | Inhibited colon shortening, decreasing the mortality rate, declined the abundance of cecal Oscillospira, associated genes | ↑: ↓: Scd1, Fabp4, Mgll, Acaa1b | [72] | |
In vitro: 0–10 mg/mL, 0–72 h In vivo: 0–300 mg/kg/day, 14 days | In vitro: HT-29 and HCT-116 cell lines In vivo: xenograft mice | Reduced cell viability, induced autophagy, decreased tumor growth, and volume | ↑: LC3-II, GFP-LC3 puncta ↓: - | [85] | |
In vitro: 0–0.32 mg/mL, 24 h In vivo: 0–300 mg/kg/day, 14 days | In vitro: HT-29 cell lines In vivo: xenograft mice | Reduced inflammation | ↑: ↓: COX-2, IL-1β, IL-6, iNOS, TNF-α, JNK, ERK | [33] | |
In vitro: GLPs: 3 μg/mL, 72 h Paclitaxel: 0.5 μM, 72 h In vivo: 2 mg/kg/day, 30 days | In vitro: CT26 and HCT-15 cell lines In vivo: xenograft mice | Reduced cell growth and viability, inhibited tumor growth, and triggered apoptosis | ↑: α-catenin, p53 ↓: IL-1β, IL-11, Cox-2 | ||
Gastric | In vivo: 400 and 800 mg/kg/every two days, four weeks | In vivo: Wistar rats bearing gastric cancer | Reduced inflammation and increased antioxidant activity | ↑: IL-2, IL-4, IL-6, CAT, GSH-Px, SOD ↓: IL-6 and TNF-α | [84] |
In vitro: 0–15 mg/mL | In vitro: AGS cell lines | Reduced cell viability, promoted apoptosis and autophagy | ↑: cleaved-PARP, LC3-II, p62 ↓: Bcl-2, pro-caspase-3 | [143] | |
Glioma | In vivo: 0–200 mg/kg/day, two weeks | In vivo: male Fischer rats bearing glioma | Reduces tumor size, and modulated host immune responses | ↑: IL-2, TNF-α, INF-γ ↓: - | [113] |
Hepatocellular | In vivo: 0–200 mg/kg/day, four weeks | In vivo: xenograft mice | Inhibited tumor growth | ↑: IL-2, miR-125 ↓: FoxP3, Notch1 | |
Leukemia | In vitro: 0–200 μg/mL, 0–48 h | In vitro: THP-1 cell lines | Induced apoptosis degraded DNA | ↑: TNF-α, caspase-3, caspase-7, TRAIL ↓: - | [16] |
Lung | In vitro: 0- 12.8 μg/mL, 24 h | In vitro: lung cancer plasma patients | Reduced cell proliferation | ↑: – ↓: – | [110] |
In vitro: 0–1000 μg/mL, 24 h In vivo: 2.5 g/kg/day, 14 days | In vitro: A549 cell lines In vivo: xenograft mice | Reduced the cell viability, and tumor weight, increased the immune index of serum | ↑: – ↓: – | [34] | |
In vitro: 0–300 μg/mL, 0–48 h In vivo: 75 mg/kg/every two days | In vitro: A549 cell lines In vivo: xenograft mice | Reduced the viability and mobility of lung cancer cells | ↑: – ↓: EGF, p-Akt, p-ERK1/2, p-FAK, p-Smad2, TGF-β | [39] | |
In vivo GLPs: 75 mg/kg/every two days, 20 days Cisplatin: 2.3 mg/kg/day, five days | In vivo: xenograft mice | Attenuated tumor growth and formation of nodular pulmonary metastases, induced apoptosis, and enhanced the therapeutic effects of cisplatin | ↑: – ↓: – | [88] | |
In vitro: 0–800 μg/mL, 0–72 h | In vitro: A549 and LLC1 cell lines | Alleviated the growth and viability of both cell lines | ↑: - ↓: p-Akt, p-EGFR, p-ERK, p-Smad2, p-FAK, Slug, twist, TGFβRII | [89] | |
Oral | In vitro: 0–800 μg/mL, 0–72 h | In vitro: SAS cell lines | Declined the viability of cells, suppressed the cell cycle, prompted apoptotic responses, reduced cytotoxicity of cisplatin | ↑: Bax/Bcl-2 ratio ↓: p-Akt, p-EGFR | [38] |
In vitro: 0.01- 15 mg/mL, 72 h | In vitro: SCC-9 cell lines | Reduced the viability and colony formation of SCC-9 cells, delayed cell migration, and inhibited EMT development | ↑: - ↓: ABCG2, AXL, N-cadherin, p75NGFR Twist, Vimentin | [18] | |
Ovarian | In vivo: 100–300 mg/kg/ twice a day | In vivo: ovarian cancer rats | Reduced malondialdehyde formation and increased the total antioxidant capacity | ↑: SOD, CAT, GSH ↓: - | [131] |
In vitro: 0–10 μg/mL, 0–3 days | In vitro: OVCAR-3 cell lines | Reduced cell growth and viability and inhibited the cell cycle | ↑: CAT, SOD, NQO1, GSTP1, DJ1, Trx, Nrf-2 ↓: cyclin D1 | [36] | |
Prostate | In vitro: 0–20 μg/mL, 0–120 h | In vitro: LNCaP cell lines | Reduced cell proliferation and migration,, suppressed the cell cycle at the G1 stage | ↑: p21 ↓: PRMT6, CDK2, FAK, SRC | [138] |
In vitro: 1.25–10 mg/mL, 0–72 h | In vitro: PC-3 cell lines | Reduced the cell viability, stimulated late apoptosis | ↑: NAG-1, cleaved PARP ↓: pro-caspase-3, -6, and -9, p-Akt, p-MAPK/ERK | [120] | |
Sarcoma | In vivo: 0–100 mg/kg/day, 21 days | In vivo: xenograft mice | Reduced the tumor growth and size | ↑: – ↓: – | [25] |
Skin | In vivo: 33.3–300 mg/kg/day, eight days | In vivo: xenograft mice | Inhibited tumor growth | ↑:– ↓:– | [86] |
Breast cancer
Cervical cancer
Impact of GLPs on cervical cancer: an in vivo setting
GLPs as adjunct to cisplatin in cervical carcinoma
Effect of GLP on cervical cancer cells: an in vitro approach
Effect of GLP on colon and colorectal cancer
Impacts of GLPs on cell cycle and apoptosis
Autophagy-inducing and anti-inflammatory effects of GLPs
Chemo-Sensitization effects of GLPs
Effect of GLP on Gastric cancer
Interactions between GLPs and Glioma cancer
Imacts of GLPs and Hepatocellular carcinoma
Effects of GLPs on Leukemia
GLPs in lung cancer management
Oral cancer and the promising role of GLPs
Ovarian cancer and GLPs as a therapeutic agent
Ovarian Cancer and the Antioxidant Effects of GLPs
G. lucidum extract and ovarian cancer cells
Effect of GLPs on Prostate cancer
Impact of GLPs on Sarcoma
Interaction between GLPs and skin cancer cells
Clinical Studies on GLPs and immune function in cancer patients
Application of G. lucidum polysaccharides as nanoparticle delivery system
Studies on GLPs-based NP delivery systems
Drug | Particle size (nm) | Preparation method | Applied Cell type/Animal | Entrapment Efficacy (%) | Results | Refs. |
---|---|---|---|---|---|---|
CS-GLPs | 217 ± 6 | ion-revulsion | HepG2, HeLa and A549 cell lines (0- 6 μg/mL, 24 h) | 25.01 | The NPs containing GLP exhibited more pronounced tumor suppression and enhanced growth-promoting effects compared to the free GLP solution | [60] |
SeNP-SGLP | 25 | Chemical resuction and dispersion | Raw 264.7 cell lines (0–100 μg/mL, 0–24 h) | – | The anti-inflammatory properties of SeNPs-GLPS may play a role in the ongoing efforts to combat cancer and inflammation | [115] |
GLPs microemulsion | 87.94 ± 3.17 | queous titration method | A549 and Caco-2 cell lines (0–1000 μg/mL of oil phase, 0–24 h); Xenograft mice (8 mg/kg) | – | This study elucidated the potential mechanism of the spatial relationship between GLps and microemulsion and confirms the importance of GLP in tumor accumulation and its anti-tumor effectiveness | [34] |
GLP-BiNP | 10 ± 3 | electrostatic interaction between sulfhydrated GLP and BiNP | CD40, CD80, CD86, and MHCII cell lines (0–80 μg/mL, 0–24 h); Xenograft mice (2.5 g/kg/day, 14 days) | – | GLPBiNP might offer an additional anti-inflammatory effect to counteract any potential toxicity resulting from the bismuth metal in the nanoparticles | [132] |
rGO-Fe3O4-GL-PF | 11.2 ± 4.8 | Thermal process and oxidation and chemical absorption | A549 cell lines (0.1–150 μg/mL, 24 h) | 11 | NPs held great promise to develop specialized drug delivery systems for cancer therapy | [54] |
GLP-RCPBA-DPA-DHA-HCPT | 98.49 ± 5.16 | Nanoprecipitation | MCF-7 cell lines (0.7 μg/mL, 0–72 h); xenograft mice (10 mg/kg/2 days, 8 days) | 28.34 | The formulated nanoparticles effectively eliminate cancer cells, impede tumor progression, and result in minimal side effects | [142] |
Gold NPs | 38.3 ± 0.3 | Chemical reduction | CD40, CD80, CD86, and MHCII cell lines (0–40 μg/mL, 0–24 h); Xenograft mice (30 mg/kg/4 days, 12 days) | – | GLPs have the potential to be integrated into nanocomposites with immunoregulatory properties, thereby improving their effectiveness in cancer therapy | [137] |
Gold NPs | 25–29 | Chemical reduction | HT-29 cell lines | – | The apoptotic effects on cancer cells were found to increase in a dose-dependent manner when treated with Gold NPs | [21] |
EC-GLT-PVA-GLPs | 221–253 | layer-by-layer electrospinning | SGC-7901, A549, Hela and Caco-2 cell lines | 7.9 | This nanomedical film exhibited a promising antitumor effect at the cellular level | [71] |
APBA − MTX/HCPT-GLP | 191 nm | Nanoprecipitation | MCF-7 cell lines xenograft mice | 21.5 | In vivo, the GLP-APBA-MTX/HCPT nanoparticles demonstrated more potent tumor-inhibiting effects with fewer associated side effects than free MTX and HCPT | [141] |