Abstract.Fighting cancer is considered one of the most important areas of research in medicine and immunology. Due to the ability of cancer cells to mutate and become resistant to available drugs, new scientific approaches, focused on molecular mechanisms of carcinogenesis, are needed. A new direction in cancer treatment has arisen, devoted to the adjuvant use of natural bioactive compounds in conventional chemotherapy. This kind of research is gaining more attention. In particular, fungi can be used not only as strong immunoceuticals but also as a source of potent metabolites, capable of penetrating cell membranes and interfering with particular signal transduction pathways linked to processes such as inflammation, cell differentiation and survival, carcinogenesis, and metastasis. One such a crucial pathway involved in the above-mentioned processes, is the activation of the nuclear transcription factor κB (NF-κB). This review compiles the available data on fungal metabolites, known to modulate the activity of NF-κB, thus demonstrating their potential use as novel anti-cancer agents in the rapidly advancing field of molecular therapy.
Contents1. Introduction 2. Fungal metabolites modulating NF-κB activity 3. Perspectives
IntroductionCancer is the second most predominant cause of death in the modern world, after cardiovascular diseases, taking many human lives every year. Depending on the stage of cancer progression, treatments include surgical operation, radiotherapy and chemotherapy. However, their side effects cause serious damage and suffering to patients. As an alternative to these treatment methods, immunotherapy is now gaining more attention than ever. Immunotherapy substantially reduces the side effects and the inherent pain of cancer sufferred by patients and helps to overcome cancer growth, even in the last stages of the disease.Despite the observed success of most of the chemotherapeutic regimes, cellular adaptations have enabled tumor cells to evade many of these drugs. The nuclear transcription factor κB (NF-κB) is one of the factors responsible for cellular chemoresistance. It is a dimeric transcription factor belonging to the Rel/NF-κB family of transcription factors (1-4). The NF-κB complex is maintained in the cytoplasm in an inactive form by the inhibitory protein κB (IκBα), belonging to a family of inhibitory proteins, IκBs. The major activator of NF-κB is the IκB kinase complex (IKK). This complex is composed of two catalytic subunits, IKK-α and -ß and a regulatory subunit, IKK-γ (also known as NEMO) (2). The NF-κB pathway is triggered by bacterial and viral infections as well as pro-inflammatory cytokines and chemokines [e.g., tumor necrosis factor α (TNF-α), lipopolysaccharide (LPS), interleukins (IL-1, IL-6)], all of which activate the IKK complex. After activation, the IKK complex phosphorylates NF-κB-bound IκBs, thereby targeting them for proteasomal degradation. Simultaneously, the NF-κB dimers are released and free to enter the nucleus where transcriptional activation of target genes be...