Boric and Phenyl Boric
Acids Induce Apoptosis in Both Prostate Cancer and Breast
Cancer Cell Lines
Susan L Meacham, et al.
The FASEB Journal, 2007;21 :244.1.
Studies have reported that boron had beneficial effects
on embryogenesis in fish and rats and mineral metabolism in
chickens. In a typical adult human diet, daily intakes of
boron were reported to be approximately 1 - 2 mg/day. The
major form of boron in humans is boric acid, a weak acid,
mostly unionized at physiological pH. Recent reports have
indicated that boric acid is able to inhibit the growth of
prostate cancer cell lines and tumors. Our studies confirm
growth inhibition of the DU-145 and PC-3 human prostate
cancer cells lines. In addition, we have observed that boric
acid is also capable of inhibiting the growth of two human
breast cancer cell lines ZR-75-1 and SK-BR-3. In addition
to growth inhibition it was observed that boric acid and
phenyl boric acid were able to cause both the breast and
prostate cancer cells to detach and undergo apoptosis. Flow
cytometery indicated that the floating cells were
undergoing apoptosis in a dose dependent manner. A caspase 3
assay further confined apoptosis. Both boric acid and phenyl
boric acid were able to inhibit the attachment of DU-145 in
the absence or presence of MnCl2. Cell
attachment is controlled by the integrin proteins hence, our
working hypothesis is that boric and phenyl boric acids
are binding to the integrin proteins, causing the cells to
detach and undergo apoptosis.
Iron Deficiency Increases
Zip14 Expression in Hepatocytes
Hyeyoung Nam, et al.
The FASEB Journal, 2007 ;21 :859.5.
Zipl4, a member of the ZIP family of metal ion
transporters, has recently been shown to transport both zinc
and iron
(Liuzzi et aI., PNAS, 2006). Studies using mouse liver
reveal that Zip 14 mRNA levels correlate strongly and
positively with transferrin receptor (TfR) mRNA levels,
suggesting that Zip14 transcript levels increase as cellular
iron levels decrease. The aim of this study was to examine
the effect of iron deficiency on Zip14 mRNA levels in
AML12 cells, a mouse hepatocyte cell line. AML12 cells were
incubated for 24 h in medium lacking or containing an
iron chelator (50 μM of either desferrioxamine, DFO, or
salicyladehyde isonicotinoyl hydrazone, SIH). Levels of
Zip14 and TfR mRNA were assessed by quantitative RT-PCR. DFO
and SIH treatments depleted cellular iron, as
indicated by 3- to 4-fold increases, respectively, in TfR
mRNA abundance. Levels of Zip14 short isoform mRNA
increased by 60% (P<O.OI) in DFO and SIR-treated cells,
whereas levels of Zip14 long isoform mRNA increased
by nearly 200% (P<O.OI). These observations suggest that
Zip14-mediated iron/zinc transport into hepatocytes
increases in response to iron deficiency.
The Role of Zinc (Zn)
and Metallothionein (MT) in Dextran Sulfate Sodium (DSS)-
Induced Colitis in MT-Null (MT-/-) and Wild-Type Mice
Cuong D Tran, et al.
The FASEB Journal, 2007;21:861.4.
Zinc (Zn) and its binding protein metallothionien (MT) have
been proposed to suppress the disease activity of
ulcerative colitis. The aim of the present is to determine
the role of Zn and MT in the dextran sulfate sodium (DSS)-
induced model of colitis in mice. A DSS dose-response study
was conducted in male wild-type (MT+/+) and MTnull
(MT-/-) mice by supplementing 2%, 3% and 4% DSS in the
drinking water for 6 d. In the intervention study,
colitis was induced by 2% DSS, Zn (24 mg/ml as ZnO) was
gavaged (0.1 ml) daily, concurrent with DSS
administration, and the disease activity index (DAI) scored
daily. Histology, MT levels and myeloperoxidase (MPO)
activity were determined. DAI was increased (by 16% and 21 %
with 3% and 4% concentrations of DSS, respectively
compared to 2%, evident after 5 d of DSS administration. MPO
activity was increased in MT+/+ compared to
MT -/- mice and those receiving DSS. Zinc administration had
a 50% lower DAI compared to DSS alone. Zinc
partially prevented the distal colon of MT+/+ by 47% from
DSS-induced damaged compared to MT-/- mice. MT
did not prevent DSS-induced colitis and Zn was partially
effective in amelioration of DSS induced colitis.
Effects of Cd on the Subcellular
Localization of Transition Metals in
Saccharomyces Cerevisiae
Nathan H Zahler, et al.
The FASEB Journal, 2007;21:836.12.
Cd is a toxic heavy metal found in industrial contamination
and cigarette smoke. While the clinical effects
of Cd toxicity are well characterized, their cellular
origins remain unclear. One proposed mechanism for
cellular Cd toxicity is the displacement of Fe and Zn from
metalloproteins. To better understand the impact
of Cd on metal homeostasis, we have studied the effect of Cd
on the concentrations and localizations of
elements including P, S, K, Mn, Fe, Ni, Cu, and Zn in S.
cerevisiae using X-ray nanoprobe imaging. For
yeast grown in minimal media in the absence of Cd, P, K, and
Mn are concentrated in the vacuole; Fe and
Zn are concentrated in both the vacuole and the nucleus; and
Cu and S are distributed throughout the cell.
Consistent with previous studies, upon exposure to Cd we
observe an increase in the overall cellular
concentration of Zn and Fe; however, there is no change in
the distribution of Fe and Zn. In contrast, we
observed a marked redistribution of Cu to the periphery of
buds and bud-necks of dividing yeast when Cd is
added to the media. This result demonstrates that Cd impacts
Cu metabolism and suggests that
displacement of Cu from metalloproteins may also be a factor
in cellular Cd toxicity.
Low
Serum Selenium Concentrations Are Associated With Poor
Grip
Strength Among Older Women Living in the Community
Justine Beck, et al.
The FASEB Journal, 2007;21:696.2.
Increased gastrointestinal absorption and urinary
excretion of zinc has been confirmed in experimental and
clinical studies on primary arterial hypertension as a
result from changes of intracellular and extracellular
zinc content. In arterial hypertension, the levels of
zinc in serum, lymphocyte, and bone decrease while
increasing in heart, erythrocytes, kidney, liver,
suprarenal glands and spleen. These changes result in
the
loss of zinc homeostasis that leads to various degrees
of deficiency, not entirely compensated by nutritional
factors or increased absorption in the gastrointestinal
tract. Loss of zinc homeostasis can be both cause and
effect of high blood pressure. In the present review,
the role of zinc metabolism changes and its mechanisms
in arterial hypertension are discussed.
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