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TMAZ Nanoparticles as Potential Drugs Influencing the Cellular Signal Transduction Pathways

S. Ivkovic, T. Baranek, P. Bendzko and J. Schulz
Klinomed Institut für Angewandte Nanotechnologie und Nanomedizin GmbH, DE

Keywords:
klinoptinolith, nanoparticles, oxidative stress, antioxidants, cancer

Abstract:
Currently, various antioxidants are under clinical investigation as an adjunct to standard and experimental cancer therapies. Anti-cancer activity of antioxidants may not only be attributed to their radical scavenger properties, but also to direct modulation of cellular signal transduction pathways, resulting in growth arrest and apoptosis of cancer cells. Recently, it has been shown that 4 weeks of oral supplementation with tribomechanically activated zeolite (TMAZ), which is a potent antioxidant volcanic mineral, resulted in restoration of previously increased antioxidant levels (Randox Total Antioxidant Status) and decreases of free radicals (d-ROM-s Free Radical Analytical System) in plasma of cancer patients. Beside its antioxidant capacity, TMAZ demonstrated anticancer activity in in vitro tissue cultures by inhibition of protein kinase B (c-Akt) and induction of expression of p21WAF1/CIP1 and p27KIP1 tumor suppressor proteins, independently from p53 protein. Blockade of cell growth has been shown in several cancer cell lines. Moreover, TMAZ treatment of mice and dogs, suffering from a variety of cancers, led to improvement in overall health status, prolongation of survival, and decreases in tumor size. The combination of TMAZ with doxorubicin for the treatment of mammary carcinoma-bearing mice was significantly more effective in reducing the number of pulmonary metastases when compared to doxorubicin mono-therapy. Clinical observations suggest that TMAZ may be particularly promising in tumors known to respond to immune treatment with interferons and interleukins, like melanoma, renal cell cancer, lung cancer, and grade II and III astrocytoma. Significant improvements of the Karnofsky index have been demonstrated in 40 lung cancer patients and in 21 individuals suffering from glioblastoma after a 4-week treatment with 12-16 g of TMAZ daily. Some patients with melanoma stage III and IV or lung cancer survived relapse-free for five years and up to six years, respectively, on a long-term treatment with high-dose TMAZ. Prospective clinical trials are warranted to verify these encouraging data from case reports.

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