Reversal of the TPA‐induced inhibition of gap junctional intercellular communication by Chaga mushroom (Inonotus obliquus) extracts: Effects on MAP kinases

Abstract

Chaga mushroom (Inonotus obliquus) has continued to receive attention as a folk medicine with indications for the treatment of cancers and digestive diseases. The anticarcinogenic effect of Chaga mushroom extract was investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 normal rat liver epithelial cells. The cells were pre-incubated with Chaga mushroom extracts (5, 10, 20 microg/ml) for 24 h and this was followed by co-treatment with Chaga mushroom extracts and TPA (12-O-tetradecanoylphorbol-13-acetate, 10 ng/ml) for 1 h. The inhibition of GJIC by TPA (12-O-tetradecanoylphorbol-13-acetate), promoter of cancer, was prevented with treatment of Chaga mushroom extracts. Similarly, the increased phosphorylated ERK1/2 and p38 protein kinases were markedly reduced in Chaga mushroom extracts-treated cells. There was no change in the JNK kinase protein level, suggesting that Chaga mushroom extracts could only block the activation of ERK1/2 and p38 MAP kinase. The Chaga mushroom extracts further prevented the inhibition of GJIC through the blocking of Cx43 phosphorylation. Indeed cell-to-cell communication through gap junctional channels is a critical factor in the life and death balance of cells because GJIC has an important function in maintaining tissue homeostasis through the regulation of cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Thus Chaga mushroom may act as a natural anticancer product by preventing the inhibition of GJIC through the inactivation of ERK1/2 and p38 MAP kinase.

Identification of a novel blocker of IκBα kinase activation that enhances apoptosis and inhibits proliferation and invasion by suppressing nuclear factor-κB

“…These results are in agreement with those of Markaverich et al (15) who showed that DBL also downregulates cyclin D1 and c-myc levels and that it finally leads inhibition of cell proliferation in estrogen receptorpositive and estrogen receptor -negative cells. Previous reports suggest that DBL inhibits proliferation of cells and induces apoptosis in various tumor cells (15,40). It is possible that these effects of DBL are mediated through the down-regulation of antiapoptotic gene products and cyclin D1 and c-myc as described here.…”

Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease

“…The Chaga mushroom, Inonotus obliquus, is a fungal parasite, which is claimed to have natural beneficial properties for human health such as anti-bacterial, anti-allergic, anti-inflammatory and antioxidant activities protecting cell components against free radicals [21]. In a model system for gap junctional intercellular communication (GJIC), its extract has been shown to prevent the inhibition of GJIC in WB-F344 normal rat liver epithelial cells through the inactivation of ERK1/2 and P38 MAP kinases [26]. From the sclerotia of the Chaga mushroom various lanostane-type triterpenoids like inotodiol can be isolated.…”

Review on Chaga Medicinal Mushroom, Inonotus obliquus (Higher Basidiomycetes): Realm of Medicinal Applications and Approaches on Estimating its Resource Potential

“…Zhong et al 43 described an effect of growth inhibition of lung carcinoma cells by inotodiol triterpenoid. An anti-cancerogenic effect of I. obliquus tinctures was studied also by Burczyk et al, 44 Lee et al, 45 Youn et al, 46 Nomura et al, 47 Chung et al, 48 Nakajima et al, 49 and Park et al 50 In the cited works, a positive antitumor action of I. obliquus extracts was demonstrated in hepatoma, leukemia, colon, and cervical carcinomas. Nakajima et al 49 show that phenolic compounds of metanolic I. obliquus extract demonstrate a target toxicity against several lines of cancer cells and the absence of cytotoxic effects against normal cells.…”