Natural zeolite clinoptilolite: new adjuvant in anticancer therapy.
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.
Pavelić
K
K
Ruder Bosković Institute, Division of Molecular Medicine, Zagreb, Croatia. pavelic@rudjer.irb.hr
Hadzija
M
M
Bedrica
L
L
Pavelić
J
J
Dikić
I
I
Katić
M
M
Kralj
M
M
Bosnar
M H
MH
Kapitanović
S
S
Poljak-Blazi
M
M
Krizanac
S
S
Stojković
R
R
Jurin
M
M
Subotić
B
B
Colić
M
M
D000277:Adjuvants, Pharmaceutic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis; D004283:Dog Diseases / Q000188:drug therapy / Q000473:pathology; D004285:Dogs; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000032:analysis; D017641:Zeolites / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000277:Adjuvants, Pharmaceutic; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; C493961:Cdkn1b protein, mouse; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C083175:clinoptilolite; D017641:Zeolites; D050760:Cyclin-Dependent Kinase Inhibitor p27; C494918:AKT1 protein, human; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt