Inhibitory effect of zinc on human prostatic carcinoma cell growth

Liang, J. Y.; Liu, Yiyan; Zou, Jing; Franklin, Renty B.; Costello, Leslie C.; Feng, Peng

doi:10.1002/(sici)1097-0045(19990801)40:3<200::aid-pros8>3.3.co;2-v

Cited by 45 publications

(63 citation statements)

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“…Noteworthy, zinc and zinc transporters play an important role in the molecular pathogenesis of prostate cancer; in particular, Zip-1, Zip-2 and Zip-3 are down-regulated in prostate cancer with a loss of the capability to accumulate zinc in the malignant cells. This a defense mechanism of tumor cells because zinc induces G2/M phase arrest and apoptosis in prostate cancer cells [52]. Therefore, Zip-1, Zip-2 and Zip-3 are suggested as tumor suppressor genes and zinc as a tumor suppressor agent [53].…”

Section: Discussionmentioning

confidence: 99%

“…This method may be a useful tool to estimate the rate of intracellular zinc homeostasis and its role in inflammatory/immune response in aging or other age-related diseases in which intracellular zinc homeostasis is involved, such as cancer, cardiovascular diseases and diabetes type 2 [20,38,52,53]. However, it does not exclude that age-related immune cell variations, especially in very old age, may play a role.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of intracellular zinc signals in nonadherent lymphocytes from young-adult and elderly donors: role of zinc transporters (Zip family) and proinflammatory cytokines

Giacconi

Malavolta

Costarelli

et al. 2012

The Journal of Nutritional Biochemistry

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison of intracellular zinc signals in nonadherent lymphocytes from young-adult and elderly donors: role of zinc transporters (Zip family) and proinflammatory cytokines

Giacconi

Malavolta

Costarelli

et al. 2012

The Journal of Nutritional Biochemistry

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“…43,44 In fact, zinc at low concentrations below 200 µM induces cell death, while at high unphysiological concentrations it suppresses the apoptotic cell death. [43][44][45][46][47][48] The present study demonstrates that zinc at low concentration induced activation of p53 protein and ROS generation in MCF7 cells. It has also been reported that Zn 2+ triggered prolonged mitochondrial ROS production 49,50 that might be a result of inhibition of the electron transport chain, presumably bc1 complex.…”

Section: Discussionmentioning

confidence: 99%

Role of p53 and reactive oxygen species in apoptotic response to copper and zinc in epithelial breast cancer cells

Ostrakhovitch

Cherian

2005

Apoptosis

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Previous studies revealed that cells may differ in their response to metal stress depending on their p53 status; however, the sequence of events leading to copper-induced apoptosis is still unclear. Exposure of copper (10 and 25 microM) and zinc (10 and 25 microM) caused activation of p53 in ER+/p53+ human epithelial breast cancer MCF7 cells and resulted in up-regulation of p21. Transactivation of p53 in MCF7 cells also led to increase in expression of Bax, proapototic Bcl-2 family member, triggering mitochondrial pore opening, and PIG3 (p53-induced gene 3 product), and also generation of intracellular reactive oxygen species (ROS). The treatment of MCF7 cells with either copper or zinc for 4 h also caused decrease in mitochondrial membrane potential (Delta psi(m)), accompanied by an elevation in the ROS production and redistribution of p53 into mitochondria. The loss of Delta psi(m) was correlated with accumulation of Annexin V positive apoptotic cells. However, the release of apoptosis inducing factor (AIF) and its translocation into nucleus was observed only in MCF7 cells treated with copper. In MDA-MB-231 (ER-/p53-) and MCF7-E6 (ER+/p53-) cells, both p53 and p21 protein levels were not altered in the presence of metals. These cells were resistant to metals, and there was no alteration in Delta psi(m). Copper treatment did not result in accumulation of ROS in these cell lines with an inactive p53 even after exposure to 50 microM of copper for 6 h, indicating a key role for p53 in the ROS generation. Pretreatment of MCF7 cells with p53 inhibitor, pifithrin-alpha, resulted in decrease of copper and zinc induced ROS production to the control level, suppression of both Bax expression and AIF release. Therefore, the activation of p53 seems to play a crucial role in copper and zinc induced generation of ROS in epithelial breast cancer cells, and expression of downstream targets of p53, such as PIG3 and Bax, responsible for increased generation of the intracellular ROS, as well as disruption of mitochondrial integrity. Our data suggest that copper induces apoptosis in MCF-7 cells with no caspases through the depolarization of mitochondrial membrane with release of AIF and its translocation into the nucleus. The results demonstrate that a functional p53 is required for the execution of apoptosis in epithelial cells.

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“…Osteopontin has also been involved in cell migration as an integral component of CD44-ERM [111] and CD44 variant 6 that has also been demonstrated in PCs [112]. In addition, PCs store zinc that has been implicated in coordinate regulation of mitosis and apoptosis [113,114]. However, PCs do not seem indispensable for crypt formation, since in mice with ablated PCs small intestinal crypts appear morphologically normal [51].…”

Section: The Role Of Pcs In Crypt Development and Homeostasismentioning

confidence: 99%

The multifaceted Paneth cell

Porter

Bevins

Ghosh

et al. 2002

Cellular and Molecular Life Sciences (CMLS)

358

275

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Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts, the 'crypts of Lieberkühn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive granule-staining pattern. Early on, PCs were proposed to perform a specialized function other than absorption of digested nutrients, the predominant task of the small intestinal epithelium. Since then, many constituents of the PC granules have been biochemically characterized. The presence of various granule-associated antimicrobial substances and their release upon microbial challenge suggest that PCs function as specialized defense cells in the small intestine. Altered resistance to microbial infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs. Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development, digestion, and intestinal inflammation.

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Inhibitory effect of zinc on human prostatic carcinoma cell growth

Cited by 45 publications

References 0 publications

Comparison of intracellular zinc signals in nonadherent lymphocytes from young-adult and elderly donors: role of zinc transporters (Zip family) and proinflammatory cytokines

Comparison of intracellular zinc signals in nonadherent lymphocytes from young-adult and elderly donors: role of zinc transporters (Zip family) and proinflammatory cytokines

Role of p53 and reactive oxygen species in apoptotic response to copper and zinc in epithelial breast cancer cells

The multifaceted Paneth cell

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