Zinc as an anti-tumor agent in prostate cancer and in other cancers

Franklin, Renty B.; Costello, Leslie C.

doi:10.1016/j.abb.2007.02.033

Cited by 211 publications

(161 citation statements)

References 62 publications

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“…zinc levels three to 10-fold higher than in other soft tissues [120][121][122]). As a consequence, citrate accumulates and is excreted into the prostatic fluid.…”

Section: Early Stage Prostate Cancer Metabolismmentioning

confidence: 85%

“…As a consequence, citrate accumulates and is excreted into the prostatic fluid. In an early step during the transition from healthy to malignant tissue, prostate cells lose their ability to accumulate zinc due to the downregulation of zinc transporters (mainly ZIP1) [122,123]. Therefore, the block of the tricarboxylic acid cycle is relieved and the cells switch their metabolism to generate energy via oxidation of citrate and coupled respiration.…”

Section: Early Stage Prostate Cancer Metabolismmentioning

confidence: 99%

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Organ-Specific Cancer Metabolism and Its Potential for Therapy

Elia

Schmieder

Christen

et al. 2015

Handbook of Experimental Pharmacology

104

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KEYWORDS:Cancer metabolism, metabolic therapy, tissue specific metabolism, genetic drivers, epigenetic drivers, microenvironment, Warburg effect, reverse Warburg effect, mixed Warburg effect, triple-negative breast cancer, estrogen receptor positive breast cancer; prostate cancer, liver cancer, gluconeogenesis, fatty acid metabolism, glucose metabolism, glutamine metabolism, serine metabolism, metabolic normalization, metabolic depletion ABSTRACTTargeting the metabolism of cancer cells has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor positive breast cancer, early and late stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g. Warburg versus reverse Warburg metabolism). Yet, for each of the cancers their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion.

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“…zinc levels three to 10-fold higher than in other soft tissues [120][121][122]). As a consequence, citrate accumulates and is excreted into the prostatic fluid.…”

Section: Early Stage Prostate Cancer Metabolismmentioning

confidence: 85%

Section: Early Stage Prostate Cancer Metabolismmentioning

confidence: 99%

Organ-Specific Cancer Metabolism and Its Potential for Therapy

Elia

Schmieder

Christen

et al. 2015

Handbook of Experimental Pharmacology

104

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“…Since the early Mawson 16 innumerable studies consistently demonstrated that zinc levels and citrate levels are markedly decreased (~60-90%) in prostate cancer as compared with normal and benign prostate. [1][2][3][4] For example normal prostate peripheral zone (where most malignancies arise and develop) contains approximately 3,000 nmols zinc/gm tissue, as compared with 600 nmols/gm in cancer. The citrate levels are approximately 13,000 and 1,000 for normal vs. cancer.…”

Section: Discussionmentioning

confidence: 99%

“…It is well established that zinc and citrate levels are virtually always markedly decreased in prostate cancer as compared with normal and benign prostate (for reviews see ref. [1][2][3][4]. This relationship currently, in our view, is the most consistent and persistent "hallmark" characteristic of human prostate cancer, which distinguishes prostate cancer from normal and benign prostate.…”

Section: Introductionmentioning

confidence: 98%

Human prostate cancer ZIP1/zinc/citrate genetic/metabolic relationship in the TRAMP prostate cancer animal model

Costello

Franklin

Zou

et al. 2011

Cancer Biology & Therapy

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Prostate cancer is the second leading cause of cancer deaths among men. The availability of animal models that represent the events and factors that exist in the natural history and biology of human prostate cancer is essential in dealing with prostate cancer. In recent decades and presently, emphasis has been directed at the development and employment of prostate cancer induced in transgenic mice. However, the important consistent hallmark characteristic and event of decrease in zinc and citrate and downregulation of ZIP1 zinc transporter in prostate malignancy has not been studied or identified in any animal model. We investigated the status of these parameters in TRAMP tumors as compared with human prostate cancer. The results show that citrate levels are markedly decreased in the developing and advancing stages of malignancy in TRAMP. Zinc levels are also decreased and ZIP1 transporter is lost in TRAMP tumors. In vitro studies show that zinc treatment of TRAMP C2 cells exhibits cytotoxic effects. Collectively, these results mimic the ZIP1, zinc, and citrate status and relationship that exist in human prostate cancer. This is the first report that establishes the existence of the human prostate zinc/citrate hallmark characteristic and relationship in an animal model. It now appears that the TRAMP model will be suitable for studies relating to the implications and role of zinc-and citraterelated metabolism in the development and progression of human prostate cancer.

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“…[2][3][4] In such cancers, the zinc levels of malignant tissue are markedly decreased as compared with the normal tissue. At this pancreatic adenocarcinoma is an untreatable deadly cancer.…”

Section: Introductionmentioning

confidence: 99%