Iodine Uptake and Prostate Cancer in the TRAMP Mouse Model

Olvera-Caltzontzin, Paloma; Delgado, Gabriela; Aceves, Carmen; Anguiano, Brenda

doi:10.2119/molmed.2013.00093

Cited by 5 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRAMP mice have been reported to exhibit a high level of nuclear TRP53 [ 19 ], but Western blot results revealed that BITC treatment did not induce the expression of p21 ( Figure 4 A) or Bax (data not shown), downstream targets of p53. Olvera-Caltzontzin et al [ 37 ] reported that iodine increased p53 mRNA expression but had no effect on p21 in tumors from TRAMP mice. TRAMP mice develop autochthonous prostatic tumors that express SV40 Tag.…”

Section: Discussionmentioning

confidence: 99%

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

Cho

Lim

Kwon

et al. 2016

IJMS

View full text Add to dashboard Cite

Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. In vitro cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.

show abstract

Section: Discussionmentioning

confidence: 99%

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

Cho

Lim

Kwon

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…An important fact to consider is that these beneficial effects occur only at relatively high iodine concentrations (milligrams/day) and only in those tissues that are able to capture iodine. In the case of mammary and prostate glands, both normal and tumoral cells internalize I 2 by a sodium/iodine symporter (NIS)-independent mechanism [ 1 , 4 , 5 , 8 , 37 ] that seems to involve a facilitated diffusion process (saturable and dependent on protein synthesis) [ 5 ]. It has not yet been determined how I 2 reacts with cell components, but I 2 is known to bind covalently to proteins and lipids [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Activation of peroxisome proliferator-activated receptor gamma is crucial for antitumoral effects of 6-iodolactone

et al. 2015

Self Cite

View full text Add to dashboard Cite

BackgroundMolecular iodine (I2) exhibits antiproliferative and apoptotic effects on in vivo and in vitro cancer models. These effects are thought to be mediated by an iodinated arachidonic acid derivative, 6-iodolactone (6IL), and one of the proposed mechanisms is that 6IL activates Peroxisome Proliferator-Activated Receptors type gamma (PPARG). These receptors have been implicated in the inhibition of carcinogenic processes, in addition to their classical role in maintaining lipid and glucose homeostasis. The aim of this study was to determine whether PPARG participates in the 6IL antiproliferative and apoptotic effects on the mammary cancer cell line MCF-7.MethodsThe 6IL/PPARG complex was inhibited by the PPARG antagonist GW9662, in both an endogenous and overexpressed (adenoviral vector infection) context, and stable PPARG-knockdown MCF-7 cells (RNA interference, confirmed with hydrolysis probes and Western blot), were used to corroborate the PPARG participation. 6IL effects on proliferation (measured by Trypan Blue exclusion) and apoptosis (phosphatidylserine identification by flow cytometer) were evaluated in conditions of chemical inhibition (GW9662) and silencing (RNA interference). A wound-healing assay was conducted on wild-type and stable PPARG-knockdown MCF-7 cells to evaluate the antimigrational effect of 6IL. Caspase-8 activity was evaluated to determine if the extrinsic pathway is involved in the effects of 6IL and I2 treatment.ResultsAntiproliferative and pro-apoptotic 6IL effects require the activation of PPARG. In addition, wound-healing assays show that 6IL is able to inhibit MCF-7 cell migration and that PPARG plays a role in this phenomenon. Finally, the data exclude the participation of the extrinsic apoptotic pathway in 6IL- and I2-induced apoptosis.ConclusionsThese results support the previously proposed mechanism, in which the I2 effects are mediated by 6IL, and they provide further support for the use of I2 as coadjuvant in breast cancer treatment.

show abstract

“…These effects disappeared when the high dose of supplemental iodine was suspended [ 24 ]. Antineoplastic action of the I 2 supplement without harmful effects on the thyroid has also been observed in mammary and prostatic pathologies in preclinical (rodents and canines) and clinical protocols [ 25 , 26 , 27 , 28 ]. Although the thyroid captures 40% less I 2 than I − , the acceptable upper limits for iodine intake during pregnancy are not well defined, and the consequences of excess iodine in newborns are not well documented [ 15 ], so the iodine intake in any of its forms above the upper limits is not recommended in pregnant women or infants.…”

Section: Introductionmentioning

confidence: 99%

Molecular Iodine Has Extrathyroidal Effects as an Antioxidant, Differentiator, and Immunomodulator

Aceves¹,

Mendieta²,

Anguiano³

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Most investigations of iodine metabolism in humans and animals have focused on its role in thyroid function. However, considerable evidence indicates that iodine could also be implicated in the physiopathology of other organs. We review the literature that shows that molecular iodine (I2) exerts multiple and complex actions on the organs that capture it, not including its effects as part of thyroid hormones. This chemical form of iodine is internalized by a facilitated diffusion system that is evolutionary conserved, and its effects appear to be mediated by a variety of mechanisms and pathways. As an oxidized component, it directly neutralizes free radicals, induces the expression of type II antioxidant enzymes, or inactivates proinflammatory pathways. In neoplastic cells, I2 generates iodolipids with nuclear actions that include the activation of apoptotic pathways and the inhibition of markers related to stem cell maintenance, chemoresistance, and survival. Recently, I2 has been postulated as an immune modulator that depending on the cellular context, can function as an inhibitor or activator of immune responses. We propose that the intake of molecular iodine is increased in adults to at least 1 mg/day in specific pathologies to obtain the potential extrathyroid benefits described in this review.

show abstract

Iodine Uptake and Prostate Cancer in the TRAMP Mouse Model

Cited by 5 publications

References 42 publications

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

Activation of peroxisome proliferator-activated receptor gamma is crucial for antitumoral effects of 6-iodolactone

Molecular Iodine Has Extrathyroidal Effects as an Antioxidant, Differentiator, and Immunomodulator

Contact Info

Product

Resources

About