The founder of cellular pathology, Rudolf Virchow, defined cancer as a chronically non-healing wound. The data accumulated over the past decade indicate that among immune cells unconditioned cancer antagonists are only certain macrophage sub-populations, cytotoxic T-lymphocytes and natural killer cells, while the functions of other cellular participants of immune responses (such as neutrophils,
... [Show full abstract] mast cells, and even individual subpopulations of T- and B-lymphocytes) are diverse and, as a whole, are included in the progression of tumors. During the development of inflammatory responses, these cells propagate signaling molecules such as epithelial, endothelial and fibroblast growth factors (EGF, VEGF, FGF), chemokines and pro-inflammatory cytokines, as well as proteolytic enzymes that reduce tissue density (e.g., matrix metalloproteinases) that promote tumor invasion [1–3].
In the development of a mycotherapeutic approach, the double role of the immune system in cancer progression and tumor control, forces the profiling of the fungal bioactive complexes for both immune-stimulating and anti-inflammatory components.
The main pro-inflammatory factor, constitutionally associated with cancer progression, is the NF-κB chemokine, which blocks both JNK (c-Jun N-terminal kinases) and p53-mediated apoptotic pathways. Due to the research of Erkel’s group, from fungi such as Lentinus crinitus and some species of the genus Panus (Panus conchatus, P. lecomtei), the terpenoid panepoxidone was released, which prevents the degradation of inhibiting particles of NF-κB (IκBα) that inactivate this transcriptional factor [4]. Cyclopepoxidone was isolated from the Xylaria 45-93 ascomycete strain [5], isopanepoxidone was isolated from Panus conchatus [6], and both substances have a similar effect. In addition to panepoxidone and similar substances, the lipopolysaccharide isolated from Taiwanofungus camphoratus inhibits the degradation of the inhibiting IκBα particle [7, 8]. Mattilla’s team showed that in the fruit bodies of Lentinula edodes, caffeic acid phenethyl ester (CAPE) inhibiting NF-κB, even during the binding with DNA [9], is contained. Later, CAPE was detected in extracts of Inonotus linteus [10].
The second important direction of restraint of tumor-promoting in the immune system is the inhibition of matrix metalloproteinases. Zinc-containing endopeptidases released by a number of cancer cells and granulocytes contribute to the softening of the fibrillar and non-fibrillar connective tissue matrix, which significantly facilitates tumor invasion and metastasis. The polyporenic acid C and (E)-2-(4-hydroxy-3-methyl-2-butenyl)-hydroquinone isolated from the basidiomycetes Piptoporus betulinus and Daedalea dickinsii showed inhibitory effects on the collagenase of MMP-1, stromelysin MMP-3 and MMP gelatinase-9 [11–16].
In conclusion, it should be noted that the inhibition of processes without impact to vital targets of cancer cell is is fraught with a situation described by Swiss oncologist Pierpaoli: «In fact, automatic mechanisms exist in the body, negative for the therapy, by which the artificial inhibition induced with exogenous agents will inevitably evoke an opposite answer (promotion) which will cancel and make thus deadly for the patient the application of inhibitory factor. A strong inhibition evokes an even stronger promotion» [17]. For this reason, the fungal substances alone – without their combination with vital poisons (chemotherapy) or with radiation exposure – is not enough for cancer control on its progressive stages.
