**4. Adjuvant in anticancer treatment**

The first studies of anticancer effect of zeolites were performed at the beginning of 2001 when it was observed that the treatment with clinoptilolite of different tumors in mice and dogs have improved their life span and tumors have decreased in size [54]. *In vitro* studies using cancer cell cultures revealed the clinoptilolite inhibitory effect on protein kinase B (B-Akt), which reduced the growth of cancer cells and increased their apoptosis. Inhibition occurred only in the presence of serum. This finding suggests that adsorption of serum components may be a possible mode of action. Adsorption of molecules involved in transduction signals, such as inositol, phosphatides and Ca, can contribute to its therapeutic efficacy. It also induces expression of tumor suppressor proteins, p21 WAF1/CIP and p27 KIP1, blocking the growth of cancer cell lines. It is assumed that clinoptilolite reduces the exchange rate of intestinal epithelial cells, prolonging their activity, and that silicates and aluminosilicates can interact directly with some cells by modifying their intracellular pathways, and this leads to the alterations in the regulation of gene expression. Changing the order of interaction of other proteins with membrane proteins may be involved, since membrane transport is required to activate protein kinase B [54]. Studies in mice injected i.v. with melanoma cells but receiving a micronized zeolite through gastric intubation for 28 days, revealed an increase in allogeneic graft versus host (GVH) in lymphocytes in the lymph nodes and a reduction in pulmonary metastases. The researchers' hypothesis is that the local inflammation caused by zeolite application, attracts peritoneal macrophages, and these cells in turn produce TNFα that stimulates spleen T-cells, which amplify the local inflammatory response [55]. Also, a reduction in the metabolic rate of cancer cells and a reduced production of 4-hydroxyinonenal following an anti-cancer treatment (Doxorubicin) along with tribomechanically micronized clinoptilolite, having in this way a potentiator effect on anticancer drugs, were reported [56].

In another *in vitro* study done on mouse fibrosarcoma cells and other types of cells incubated for 24 h together with clinoptilolite researchers observed that the number of viable cells, DNA synthesis and activity of EGF-R, PKB/Akt and NFKB was reduced while apoptosis was enhanced maybe because clinoptilolite affects cellular microenvironment through mechanisms that are dependent on its characteristics [57].
