Antiproliferative and apoptotic effects of zinc–citrate compound (CIZAR®) on human epithelial ovarian cancer cell line, OVCAR-3

Bae, Seog Nyeon; Lee, Young Suk; Kim, Mi Yun; Kim, Jae Dong; Park, Lae Ok

doi:10.1016/j.ygyno.2006.02.009

Cited by 43 publications

(33 citation statements)

References 30 publications

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“…Surprisingly, no pursuant studies to corroborate and extend this potentially important observation have been reported. However, zinc treatment of malignant ovarian cells has been shown to exhibit cytotoxic effects [24,39,40]. Although more research is necessary, ovarian cancer appears to exhibit the zinc relationships as described previously for the other cancers.…”

Section: Are the Prostate Cancer–zinc Relationships Applicable To Othmentioning

confidence: 87%

Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity

Costello

Franklin

2012

Expert Review of Anticancer Therapy

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A major issue relating to many cancers is the absence of effective chemotherapeutic agents; so that most often untreatable morbidity and death are prevalent once the cancer has been detected and has advanced. The search for efficacious anticancer agents is imperative. One potential agent is zinc, which is decreased in the development of some cancers in order to avoid its cytotoxic/tumor suppressor effects on the malignant cells. This provides the basis and opportunity to employ a treatment regimen that restores elevated zinc levels in the malignant cells and elicits the cytotoxic/tumor suppressor effects of zinc. The enigma is that this approach and expectation has not reached fruition. The question is “why?”. This article provides a discussion of relevant zinc issues that need to be considered and resolved. Important areas of research are identified as being essential for the successful application of zinc cytotoxicity/tumor suppression actions for the treatment of specific cancers.

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Section: Are the Prostate Cancer–zinc Relationships Applicable To Othmentioning

confidence: 87%

Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity

Costello

Franklin

2012

Expert Review of Anticancer Therapy

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“…Conversely, p53 is clearly required for death signaling in MCF-7 breast cells where Zn-mediated apoptosis involved also oxidative stress and mitochondrial translocation of Bax (Ostrakhovitch and Cherian 2005). Similar mechanisms may be involved in ovarian cancer demise too as demonstrated in OVCAR-3 cells where Zn inhibited mitochondrial m-aconitase, increased Bax/Bcl-2 ratio and activated caspase-3 (Bae et al 2006). In pancreatic adenocarcinoma cells PaCa44, CFPAC1, Panc1, and T3M4, Zn induced oxidative stress and translocation of apoptosis-inducing factor (AIF) into the nucleus, with resulting caspase-independent apoptosis (Donadelli et al 2009).…”

Section: Introductionmentioning

confidence: 95%

Zinc pyrithione induces cellular stress signaling and apoptosis in Hep-2 cervical tumor cells: the role of mitochondria and lysosomes

Rudolf

Červinka

2010

Biometals

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Increased intracellular free zinc concentrations are associated with activation of several stress signaling pathways, specific organelle injury and final cell death. In the present work we examined the involvement of mitochondria and lysosomes and their crosstalk in free zinc-induced cell demise. We report that treatment of cervical tumor Hep-2 cells with zinc pyrithione leads to an early appearance of cytoplasmic zinc-specific foci with corresponding accumulation of zinc first in mitochondria and later in lysosomes. Concomitant with these changes, upregulation of expression of metallothionein II A gene as well as the increased abundance of its protein occurs. Moreover, zinc activates p53 and its dependent genes including Puma and Bax and they contribute to an observed loss of mitochondrial membrane potential and activation of apoptosis. Conversely, lysosomal membrane permeabilization and its promoted cleavage of Bid occurs in a delayed manner in treated cells and their effect on decrease of mitochondrial membrane potential is limited. The use of specific inhibitors as well as siRNA technology suggest a crucial role of MT-IIA in trafficking of free zinc into mitochondria or lysosomes and regulation of apoptotic or necrotic cell demise.

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“…Only 39% to 49% gap junctions as compared to normal ones have been observed in zinc-deficient rats [26,27]. The deprivation of zinc leads to altered structure and function of DNA and RNases as well as other regulatory proteins such as histones that play important role in gene expression [20,28,29]. These changes may lead to activation or repression of selective genes and result in synthesis or degradation of specific proteins thus impairing normal cell metabolism and leading to atresia.…”

Section: Discussionmentioning

confidence: 99%

Changes in Trace Elements during Follicular Atresia in Goat (Capra hircus) Ovary

Bhardwaj

Sharma

2010

Biol Trace Elem Res

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Quantitative analysis of follicular fluid and granulosa cells from small, medium and large antral atretic follicles of goat (Capra hircus) ovaries was conducted to study the alterations in trace elements viz zinc (Zn), copper (Cu), manganese (Mn), and iron (Fe). The zinc content was lower in the follicular fluid (0.993 ± 0.001, 0.935 ± 0.002, 1.321 ± 0.001 μg/ml) and granulosa cells (0.867 ± 0.002, 0.801 ± 0.001, 1.073 ± 0.002 μg/mg) of small, medium, and large antral atretic follicles respectively than their respective controls. Copper quantity was higher in the follicular fluid (0.113 ± 0.001, [Formula: see text], 0.224 ± 0.001 μg/ml) and granulosa cells (0.094 ± 0.001, 0.114 ± 0.001, 0.182 ± 0.001 μg/mg) from small, medium, and large antral atretic follicles respectively than their respective controls. Similarly, iron and manganese was also found higher in the follicular fluid and granulosa cells of small, medium, and large antral atretic follicles than their respective controls. The present study provides the basic data on trace elements that can be safely used as atretic marker and will find use in in vitro studies for fertility improvement plan. Thus, help in elevating the number of ovulations and screening of follicles to enhance the success rate in vivo and in vitro fertilization and embryo transfer technology.

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Antiproliferative and apoptotic effects of zinc–citrate compound (CIZAR®) on human epithelial ovarian cancer cell line, OVCAR-3

Cited by 43 publications

References 30 publications

Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity

Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity

Zinc pyrithione induces cellular stress signaling and apoptosis in Hep-2 cervical tumor cells: the role of mitochondria and lysosomes

Changes in Trace Elements during Follicular Atresia in Goat (Capra hircus) Ovary

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