clinoptilolite and Neoplasms

Natural silicate materials, including zeolite clinoptilolite, have been shown to exhibit diverse biological activities and have been used successfully as a vaccine adjuvant and for the treatment of diarrhea. We report a novel use of finely ground clinoptilolite as a potential adjuvant in anticancer therapy. Clinoptilolite treatment of mice and dogs suffering from a variety of tumor types led to improvement in the overall health status, prolongation of life-span, and decrease in tumors size. Local application of clinoptilolite to skin cancers of dogs effectively reduced tumor formation and growth. In addition, toxicology studies on mice and rats demonstrated that the treatment does not have negative effects. In vitro tissue culture studies showed that finely ground clinoptilolite inhibits protein kinase B (c-Akt), induces expression of p21WAF1/CIP1 and p27KIP1 tumor suppressor proteins, and blocks cell growth in several cancer cell lines. These data indicate that clinoptilolite treatment might affect cancer growth by attenuating survival signals and inducing tumor suppressor genes in treated cells.

Topics: Adjuvants, Pharmaceutic; Aging; Animals; Apoptosis; Body Weight; Cell Cycle Proteins; Cell Division; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclins; Dog Diseases; Dogs; Female; HeLa Cells; Humans; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Neoplasms; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Signal Transduction; Tumor Cells, Cultured; Tumor Suppressor Proteins; Zeolites

Clinoptilolite is a nontoxic natural zeolite with properties of an ion-exchanger and adsorbent. Earlier studies showed that clinoptilolite could be an adjuvant in cancer therapy. The aim of this study was to define effects of clinoptilolite in cell media on cell viability and activity of key proteins regulating cell survival, cell division and stress response. The number of viable cells, DNA synthesis and activity of EGF-R, PKB/Akt and NF?B was reduced, while apoptosis was increased in cells that were cultured in medium supplemneted with clinoptilolite. These results might be due to adsorbtion of some serum components such as EGF to clinoptilolite. In treated medium without serum the predominant role of clinoptilolite is that of cation exchange, likely affecting calcium levels and calcium-dependent signalling pathways. These results are in line with other data that confirm enhanced apoptosis in cells incubated in treated medium. Together, data presented here demonstrate that clinoptilolite affects cellular microenvironment through mechanisms that are dependent on adsorptive and ion-exchange characteristics of this material.

Topics: Animals; Apoptosis; Blotting, Western; Calcium; Cell Line, Tumor; Cell Survival; Chromatography, Ion Exchange; Culture Media; DNA; ErbB Receptors; Humans; Immunoprecipitation; In Vitro Techniques; Ions; MAP Kinase Kinase 4; Mice; Neoplasms; NF-kappa B; Proto-Oncogene Proteins c-akt; Signal Transduction; Tetrazolium Salts; Thiazoles; Thymidine; Time Factors; Zeolites