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Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer

Maulik R Shah1,2* email, Christopher L Kriedt3 email, Nathan H Lents4 email, Mary K Hoyer2 email, Nimah Jamaluddin2 email, Claudette Klein5* email and Joseph Baldassare3* email

Department of Otolaryngology, Saint Louis University, Saint Louis, Missouri, USA

Saint Louis University Cancer Center, Saint Louis, Missouri, USA

Department of Pharmacological and Physiological Sciences, Saint Louis University, Saint Louis, Missouri, USA

Department of Sciences, John Jay College, City University of New York, New York City, New York, USA

Department of Biochemistry, Saint Louis University, Saint Louis, Missouri, USA

author email corresponding author email* Contributed equally

Journal of Experimental & Clinical Cancer Research 2009, 28:84doi:10.1186/1756-9966-28-84

Published: 17 June 2009

Abstract

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer.


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