Identification of organoselenium compounds that possess chemopreventive properties in human prostate cancer LNCaP cells

Terazawa, Riyako; Garud, Dinesh R.; Hamada, Naoki; Fujita, Yasunori; Itoh, Tomohiro; Nozawa, Yoshinori; Nakane, Keita; Deguchi, Takashi; Koketsu, Mamoru; Ito, Masafumi

doi:10.1016/j.bmc.2010.08.019

Cited by 46 publications

(25 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…291 Following the same principle, a number of organic Se-compounds have been synthesized and tested as chemopreventive agents. 292 The production of monomethylated Se from methylselenocysteine or methylseleninic acid has been postulated as a key step in the mechanism of Sespecies anticancer activity. 293 In particular, methylseleninic acid synergizes with tamoxifen to induce caspase-mediated apoptosis in breast cancer cells.…”

Section: Male Infertilitymentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

631

451

View full text Add to dashboard Cite

Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

show abstract

Section: Male Infertilitymentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

631

451

View full text Add to dashboard Cite

show abstract

“…Nrf2 activators are being appreciated as possible pharmacological agents for PCa management. Selenium compounds have been shown to increase Nrf2 in PCa cells [37]. Further, Huang et al have shown that Nrf2 is epigenetically suppressed due to CpG hypermethylation in TRAMP mouse prostate tumors [25].…”

Section: Discussionmentioning

confidence: 99%

Methaneseleninic acid and γ-Tocopherol combination inhibits prostate tumor growth in Vivo in a xenograft mouse model

et al. 2014

View full text Add to dashboard Cite

Studies have shown that vitamin E and selenium possess antiproliferative effects against prostate cancer (PCa). However, results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) suggest that vitamin E (α-tocopheryl acetate; 400 mg) and/or selenium (L-selenomethionine; 200 μg) were ineffective against PCa in humans. It is arguable that the selected dose/formulation of vitamin E/selenium were not optimal in SELECT. Thus, additional studies are needed to define the appropriate formulations/dose regimens of these agents. Here, we investigated the effect of methaneseleninic acid (MSA; 41 μg/kg) and/or γ-tocopherol (γT; 20.8 mg/kg or 41.7 mg/kg) in Nu/J mice implanted with 22Rν1 tumors. MSA (41 μg/kg) and γT (20.8 mg/kg) combination was most consistent in imparting anti-proliferative response; resulting in a significant decrease in i) tumor volume/weight, ii) serum PSA, and iii) Ki-67 immunostaining. Further, we observed i) an upregulation of pro-apoptosis Bax and a down-regulation of the pro-survival Bcl2, and ii) an increase in pro-apoptosis Bad. Furthermore, the combination resulted in a modulation of apolipoprotein E, selenoprotein P and Nrf2 in a fashion that favors antiproliferative responses. Overall, our study suggested that a combination of MSA and γT, at lower dose regimen, could be useful in PCa management.

show abstract

“…Furthermore, both compounds were capable of inhibiting cell growth via cell cycle arrest. Related to structure activity relationship the presence of the exo-olefin (carbon-carbon double bond) as well as the aliphatic substitution at the imine part is critical for these compounds to activate Nrf2/ARE signaling (Terazawa et al, 2010). Other interesting derivatives are 2-substituted selenazolidine-4(R)-carboxylic acids ( Figure 5).…”

Section: Heterocycles Containing Seleniummentioning

confidence: 99%