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Chaga (Inonotus obliquus) and Cancer (anticancer research): evidence and sources
inferred from anticancer action
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Inonotus obliquus polysaccharide (IOP), the primary constituent of the parasitic fungus Inonotus obliquus , has anti-tumor, anti-inflammatory, anti-oxidation effects. However, the roles of IOP on colitis-associated cancer (CAC) are still unclear. Herein, we tested the efficacy of IOP using a mouse model of CAC induced by azoxymethane and dextran sulfate sodium (AOM/DSS). We confirmed that intragastric administration of IOP decreased CAC-induced body weight loss, colon tissue damage, colon shortening, and expression of proinflammatory mediators. Meanwhile, IOP treatment increased in expression of the NLRP3 inflammasome, IL-1β, and IL-18 in the colon of CAC mice. Moreover, in vitro , IOP inhibited the proliferation of SW620 colorectal cancer cells. Finally, overexpression of NLRP3 with plasmid transfection could further enhance the activation of NLRP3 inflammasome by IOP. Taken together, these results suggest that IOP suppresses the development of CAC, possibly by activation of the NLRP3 inflammasome, and reveal that IOP may be a therapeutic drug candidate for CAC.
AIMS: Cancer is a leading cause of morbidity and mortality worldwide; therefore, effective measures for cancer prevention and treatment are in constant demand. The extracts of Inonotus obliquus (Chaga mushroom) demonstrate potent anti-tumor activities and have been used to treat cancer in several countries; however, the actual effect and underlying mechanisms are still unclear. In the present study, we aimed to investigate the effects of continuous intake of aqueous extract from I. obliquus on tumor suppression. MAIN METHODS: Anticancer activity of the I. obliquus extract was examined in mouse models of Lewis lung carcinoma growth and spontaneous metastasis after 3 weeks of continuous extract intake at the dose of 6 mg/kg/day, which corresponded to that ingested daily with Chaga infusion in Japan. KEY FINDINGS: The extract of I. obliquus caused significant tumor suppressive effects in both models. Thus, in tumor-bearing mice, 60% tumor reduction was observed, while in metastatic mice, the number of nodules decreased by 25% compared to the control group. Moreover, I. obliquus extract-treated mice demonstrated the increase in tumor agglomeration and inhibition of vascularization. Interestingly, I. obliquus intake decreased body weight in middle-aged mice and increased body temperature in response to light-dark switching in mature adult mice. Furthermore, I. obliquus prevented temperature drop in mice after tumor implantation. SIGNIFICANCE: Our findings suggest that the I. obliquus extract could be used as a natural remedy for cancer suppression by promoting energy metabolism.
Background Inonotus obliquus, also known as Chaga, is a parasitic fungus growing on birches and used in traditional medicine (especially by Khanty people) to treat various health problems. In this study, we aimed to quantify the 3 metabolites frequently cited in literature, that is, betulin, betulinic acid, and inotodiol in the Chaga recently discovered in forests located in Normandy (France), and to compare their concentrations with Ukrainian and Canadian Chaga. This study also explores the cytotoxicity of the French Chaga against cancer-derived cells and transformed cells. Methods A quantification method by HPLC-MS-MS (high-performance liquid chromatography-tandem mass spectrometry) of betulin, betulinic acid, and inotodiol was developed to study the French Chaga and compare the concentration of these metabolites with extracts provided from Chaga growing in Canada and Ukraine. This method was also used to identify and quantify those 3 compounds in other traditional preparations of Chaga (aqueous extract, infusion, and decoction). Among these preparations, the aqueous extract that contains betulin, betulinic acid, and inotodiol was chosen to evaluate and compare its cytotoxic activity toward human lung adenocarcinoma cells (A549 line) and human bronchial epithelial cells (BEAS-2B line). Results French Chaga contains betulin and betulinic acid at higher levels than in other Chaga, whereas the concentration of inotodiol is greater in the Canadian Chaga. Moreover, the results highlighted a cytotoxic activity of the Chaga's aqueous extract after 48 and 72 hours of exposure with a higher effect on cancer-derived cells A549 than on normal transformed cells BEAS-2B ( P = 0.025 after 48 hours of exposure and P = 0.004 after 72 hours of exposure).
3 sources supporting Chaga for Cancer (anticancer research). Includes scientific publications, books, monographs and traditional-use references.
Mechanistic basis
This use is associated with the plant's anticancer (preclinical) action. Further evidence for that pharmacology:
The objective of this study was to determine the composition of triterpenoids in the extracts from the inner and outer parts of Inonotus obliquus and to evaluate their anti-proliferative activity against cancer cell lines (HT-29, AGS, MCF-7, and PC3). Inner and outer parts of I. obliquus were extracted with 80% methanol for 24 h. The extract was fractionated by Diaion HP-20 resin to obtain the triterpenoid fraction. Composition of triterpenoids in the fraction was analyzed by HPLC and LC-ESI-MS. Anti-proliferative activity was evaluated by MTT assay against cancer cell lines. Inotodiol and trametenolic acid were major triterpenoids in both of the inner and outer parts of I. obliquus. Inotodiol in triterpenoid fractions from the inner and outer parts of I. obliquus was 153.9 ± 15.4 mg/g (dry basis (db)) and 194.1 ± 11.5 mg/g, respectively. Trametenolic acid in triterpenoid fractions from the inner and outer parts of I. obliquus was 94.5 ± 9.15 mg/g (db) and 106.3 ± 8.23 mg/g, respectively. Triterpenoids in the outer part were significantly higher than those in the inner part. Anti-proliferative activity of the triterpenoid fraction from the outer part against AGS, MCF-7, and PC3 was also significantly higher than that of the inner part.
Polysaccharides derived from Inonotus obliquus (PIO) are known to possess multiple pharmacological activities including antitumor activity. However, the possible molecular mechanisms of these activities are unknown. In the present study, we determined the anti-metastatic potential and signaling pathways of PIO in the highly metastatic B16-F10 mouse melanoma cell line in vitro. We found that PIO suppressed the migration and invasive ability of B16-F10 cells and decreased the expression levels and activities of matrix metalloproteinase (MMP)-2 and MMP-9. In addition, PIO decreased the phosphorylation levels of extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK); PIO also decreased the expression level of cyclooxygenase (COX)‑2 and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in B16-F10 melanoma cells. These results suggest that PIO could suppress the invasion and migration of B16-F10 melanoma cells by reducing the expression levels and activities of MMP-2 and MMP-9 through suppressing MAPK, COX-2 and NF-κB signaling pathways.
The alkaline soluble polysacchride AIOPA isolated and purii¬ed from Inonotus obliquususing gel i¬ltration was subjected to composition analysis and determined for the antitumor and immunomodulatory activitives. Based on the results of high performance size-exclusion chromatography (HPSEC), gas chromatography (GC) and infra-red (IR) spectrum, AIOPA consisted of rhamnose, xylose, manose, galactose, glucose and galacturonic acid in a molar ratio of 3.09:1.61:2.06:4.45:19.7:1 with a molecular weight of 6.3 kDa. In the present study, it was found that AIOPA remarkably enhanced spleen and thymus index in mice bearing S180 sarcoma, and also stimulated LPS-induced splenocyte proliferation. Immunomodulatory activity assay in vitro indicated AIOPA could signii¬cantly enhance cellular lysosomal enzyme activity, nitric oxide (NO) formation and tumor necrosis factor-a (TNF-α) secretion in macrophages. Furthermore, AIOPA dose-dependently stimulated macrophages to produce NO through the up-regulation of inducible NO synthase (iNOS) activity and the maximal effect occurred at a concentration of 300 ug/ml by AIOPA.These data suggest that the antitumor activity of AIOPA may be associated with its potent immunostimulating effect. Key words: Inonotus obliquus, polysaccharide, immunomodulatory, antitumor.
AIM: To investigate the anti-proliferative and apoptotic effects of Chaga mushroom (Inonotus obliquus) water extract on human hepatoma cell lines, HepG2 and Hep3B cells. METHODS: The cytotoxicity of Chaga extract was screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, flow cytometry analysis, Western blot were employed to elucidate the cytotoxic mechanism of Chaga extract. RESULTS: HepG2 cells were more sensitive to Chaga extract than Hep3B cells, as demonstrated by markedly reduced cell viability. Chaga extract inhibited the cell growth in a dose-dependent manner, which was accompanied with G0/G1-phase arrest and apoptotic cell death. In addition, G0/G1 arrest in the cell cycle was closely associated with down-regulation of p53, pRb, p27, cyclins D1, D2, E, cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 expression. CONCLUSION: Chaga mushroom may provide a new therapeutic option, as a potential anticancer agent, in the treatment of hepatoma.
Protein-containing polysaccharides from Inonotus obliquus (Chaga), sclerotia and mycelia were extracted and partially purified. They were examined as potential inhibitors of the cell cycle regulatory enzymes cdc25 and cdc2/cyclin B and for their hypoglycemic effect, and the following results were obtained. The enzyme inhibitory activity and the hypoglycemic effects in normal mice were detected in both water-soluble and water-insoluble polysaccharides. The active principles were β-glucan, heteroglucan, and their protein complexes. No clear antienzymic traits were recognized by polysaccharides prepared from mycelia, but the hypoglycemic effect maintained for 3−48 h by the injection was recognized.