Host-mediated antitumor activity

Plants and microorganisms produce unique and diverse chemical stmctures, some of which act as immunomodulators (18—28). Of specimens used in traditional medicine, approximately 450 plant species have shown antiviral activity out of 4000 plants screened (19). Several tannins (20) exhibit strong inhibition of tumor promotion experimentally. Pretreatment of mice with small amounts of tannins for several days strongly rejected transplanted tumors. This activity has been claimed to be effected through enhancement of host-mediated antitumor activity. 

Adachi, K., Nanba, H., and Kuroda, H., Potentiation of host-mediated antitumor activity in mice by beta-glucan obtained from Grifola frondosa (maitake), Chem. Pharm. Bull. (Tokyo), 35, 35262-35270,1987. 

The Agrimonia pilosa herb, which contains agrimoniin (21), the first isolated dimeric ellagitannin, is used as an anti-cancer agent in Chinese medicine [10]. It is also used as an antidiarrheic and as a hemostatic agent in Japan. Agrimoniin (21) has also been subjected to detailed investigations related to its host-mediated antitumor activities [111, 112]. 

Interest in host-mediated, antitumor action of noncytotoxic polysaccharides stemmed from dissatisfaction with current cancer chemotherapy experiments. In these experiments, countless numbers of chemical compounds are being tested for their tumoricidal activities, with the aim of attaining a total kill of cancer cells. It has been the experience of clinicians, as well as of laboratory experimenters, however, that successful total kill of cancer cells is apt to include the host too. Hence, the enhancement or potentiation of host resistance emerged as a possible means of inhibiting tumor growth without... 

Besides these general activities based on chemical reactivity and structural features that are inherent in any polyphenolic substance (i.e., antioxidation and complexation) [1], ellagitannins are also capable of expressing remarkable biological activities such as potent antibacterial and antiviral activities, inhibition of mutagenicity of carcinogens and tumor promotion, as well as remarkable host-mediated antitumor effects [28, 106-108]. 

The most famous example of non-specific polysaccharide immunoadjuvants is lentinan isolated from Lentinus edodes. Since 1985, lentinan has been used as an antitumor agent. Lentinan is a (1 3)-/3-glucop)ranan bearing (1 6)-/3-glucopyranoside branches (O Scheme 1). This neutral polysaccharide suppresses the proliferation of sarcoma 180 tumors implanted subcutaneously in mice. Its antitumor activity was due to a host-mediated reaction with participation of thymus or thymus-dependent cells [1]. The lymphokines induced by this polysaccharide enhance the activity of lymphocytes (e. g., macrophages, helper T cells, and/or natural killer cells) in a dramatic manner [2,3,4,5]. Lentinan-like (1 3)-/3-glucopyranan (schizophyllan) contained in the insoluble fraction of Schizophyllum commune has the stracture shown in O Scheme 2 and is known to possess antitumor activity [6]. 

Microorganisms and fungi are an especially rich source of isoprenoids of the most diverse structures. Among these products one may find powerful toxins, compounds with antitumor and anti-inflammatory activity or antibiotics. Very little is known about their role in the host organisms. However, the broad spectrum of the observed biological activity could be taken as at least circumstantial evidence to indicate the existence of some function mediated by these products and essential to their producers. 

---