Table 2.
Pro-apoptotic effects of mushroom compounds/extracts in liver cancer via mitochondrial pathway in HCC cellular and rodent xenograft models.
| Species | Extract/ Compound | In vitro/ Animal Model | Trial Duration | Dose | Results | References |
|---|---|---|---|---|---|---|
| Agaricus blazei (FB) | Blazeispirol A | Hep 3B | 3–48 hours | 1–5 µg/mL | Casp9 and 3 activations, PARP degradation, ↓ Bcl-2 and Bcl-xL expressions, ↑ Bax expression, ↓ ∆Ψm. HtrA2/Omi and AIF release. | [261] |
| Ganoderma leucocontextum (FB) | Triterpene (GL22) | Huh7.5 | 3–24 hours | 7.5–40 µM | ↓ ATP-aerobic linked production, ↓LP and ↓ cardiolipin. CYC release, ↑ Bax/Bcl-2 ratio and up-regulation of p53. ↓ expression of FABPs. Casp3, 8, 9 and PARP cleavage. ↓ FABP4, PPARα, and PPARγ mRNA | [263] |
| Huh7.5 xenograft (BALB/C nude male mice (4 weeks of age)) | 1 week | 50 mg/kg | ↓ Tumour size. ↓PPARα, PPARγ, FABP1, 4, and 5 expression |
|||
| Ganoderma lucidum (FB) | Triterpene-rich extract | Huh-7, Chang liver cells * | 4–48 hours | 50–200 µg/mL | ↓ PKC activity. Activation of JNK and p38 MAP kinases. | [265] |
| Ganoderma lucidum, Phellinus linteus, Auricularia auricula (FB) | Polysaccharides-rich extract | HepG2, Bel-7404 | 24–72 hours | 0.25–2 mg/ml | ↓ AKT activity, ↑ PI3K and p-PTEN. ↓ Bcl-2 family protein levels. CYC and Smac release. Casp3 and 9 cleavage. | [265] |
| Grifola frondosa (FB) | Polysaccharides-rich extract | HepG2, HL-7702 * | 24 hours | 100–500 µg/mL | ↓ Bcl-2 and ↑ Bax expression/mRNA levels. ↓ ∆Ψm, ↑ CYC, casp3 and 9 protein level. | [264] |
| Pleurotus ferulae (FB) | Ethanol extract | HepG2, H22 | 24–72 hours | 1.368–8.208 µg/mL (flavonoids) | ↑ p-JNK. In H22 cells: ↑ ROS and ↓ levels of MMP-2 and -9. ↓ ∆Ψm, ↑ Bax/Bcl-2 ratio. CYC release, cleavage of casp3, 7, 9, 12 and PARP | [259] |
| H22 xenograft | 8 weeks | 2.74 or 5.48 mg/kg (flavonoids) | ↓ Tumour size. ↑ survival rate. | |||
| Pleurotus nebrodensis (FB) | Polysaccharides-rich extract | HepG2 | 48 hours | 12.5 –125 µg/mL | ↓ ∆Ψm, ↑ Bax/Bcl-2 ratio, CYC release. Casp3 and 9 activations | [25] |
| HepG2 xenograft (Kunming male mice (6–8 weeks of age)) | 4 weeks | 12.5 –125 mg/kg bw | ↓ Tumour size. ↑ Bax/Bcl-2 ratio, CYC release | |||
| Pleurotus pulmonarius (FB) | Polysaccharides/protein-rich extract | Huh7, Hep3B, WRL-68 * | 24 and 48 hours | 25–400 µg/mL | casp3 and PARP cleavage. Suppression of PI3K/AKT signalling pathway and over expression of the constitutively active form of AKT (Myr-AKT). | [266] |
| Huh7 xenograft (BALB/C nude male mice (6-8 weeks of age)) | 4 weeks | 200 mg/kg (oral), 50 mg/kg (i.p) | ↓ Tumour size. ↓ expression of p-AKT, p-GSK3b, Bcl-xL, ↑ expression of cleaved casp3 | |||
|
Tricholoma matsutake (FB) |
Aqueous extract | HepG2, SMMC-7721 | 6–48 hours | 1–5 mg/mL | ↑ casp3, 8, and 9 activities. ↑ ROS and ↓ ∆Ψm. ↑ cleaved-PARP and Bad levels, ↑ Bax/Bcl-2 ratio. | [260] |
| HepG2 or SMMC-7721 xenografts ((BALB/C nude male mice (6 weeks of age)) | 14 days | 1 g/kg | ↓ Tumour size. ↑ cleaved-PARP, Bax and Bad expression. |
FB: Fruiting bodies; * No effects were observed in the non-cancer cell lines; ↑ and ↓refer respectively to a relative increase or decrease as compared to the control group. Abbreviations: Caspase 9 (Casp9), PARP (poly (ADP-ribose) polymerase), Bcl-xL (B-cell lymphoma-extra large), Bax (Bcl-2-associated X protein), ∆Ψm (mitochondrial membrane potential), HtrA2/Omi (high temperature requirement protein A2/ stress-regulated endoprotease), AIF (apoptosis-inducing factor), ATP (adenine triphosphate), LP (lipoprotein), CYC (cytochrome C), FABPs (fatty acid binding proteins) PPARα (peroxisome proliferator-activated receptor α), PPARγ (peroxisome proliferator-activated receptor γ), PKC (protein kinase C), JNK (Jun N-terminal kinase), MAP (mitogen-activated protein), AKT (protein kinase B), PI3K (phosphoinositide 3-kinase), p-PTEN (phosphorylated-phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase), Smac (second mitochondria-derived activator of caspase), ROS (Reactive Oxygen Species), MMP-2 (matrix metalloproteinase-2), p-GSK3b (phosphorylated-glycogen synthase kinase 3 beta), Bcl-2 (B-cell lymphoma 2).