Methylseleninic Acid Research Articles

Antitumor Activity of Selenium and Search Parameters for Its New Potentially Active Derivatives

The trace element selenium is known to manifest antitumor activity. There is a relationship between the development of cancer and selenium content in food. Recent data demonstrated the necessity of increasing selenium consumption for the prevention and treatment of oncological diseases. Certain features of cancer cells and potential targets of selenium therapy are discussed. Both natural forms of selenium, namely, element Se, sodium selenite, L-selenocystine, L-selenomethionine, and L-methylselenocysteine, and synthetic ones, methylseleninic acid and imidoselenocarbamate derivatives, which display antitumor activity due to the generation of methylselenol and hydrogen selenide, the main anticarcinogenic metabolites, are reviewed. New promising anticancer selenium compounds, diacetophenonyl selenide, 2-methylselanyl-1-phenylethanol, and amino acids 2-amino-3-selanyl butanoic acid and 2-amino-3-(methylselanyl) butanoic acid are discussed.

Inhibitory Effect of Selenium on Esophagus Cancer Cells and the Related Mechanism.

Selenium has been associated with many malignant tumors including esophagus cancer (EC). In current study, we examined the effects of three types of selenium, sodium selenite (SSE), methylseleninic acid (MSA) and methylselenocysteine (MSC) on EC cell line Eca109. Here, selenium attenuated cell viability and increased cell apoptosis, especially in MSC, when compared with control group (p<0.05). Meanwhile, MSC and MSA, but no SSE, arrested cell cycle in G0/G1 phase (p<0.05). Mechanistically, FAL1 and PTEN were found to participate in regulating cell cycle and cell apoptosis process by decreasing cyclinD1, CDK2, and promoting caspase-3, caspase-8. In addition, we found that cyclinD1, CDK2 were significantly downregulated by MSA and MSC, while caspase-3, caspase-8 were dramatically upregulated by SSE (p<0.05). Based on these results, we concluded that MSC and MSA inhibit the viability of Eca109 mainly through reducing cell proliferation, while SSE by promoting apoptosis.

Effect of organo-selenium anticancer drugs on nitrite induced methemoglobinemia: A spectroscopic study.

Selenium containing drugs like selenomethionine, selenocystine, selenourea and methylseleninic acid are reported to exhibit potential anticancer effect. However, these anticancer drugs may exert adverse effects when used over a prolonged period. Little is known about the interaction of these selenium containing drugs with the vital erythroid protein hemoglobin. In this work a comparative study of the interaction of organo-selenium drugs with hemoglobin and heme moiety has been performed using different spectroscopic techniques to find out their role on drug induced methemoglobinemia. We found that though these selenium containing drugs have similar binding affinity towards hemoglobin, they have differential interactions with the heme group. Isothermal calorimetric titration study showed that selenourea has the lowest binding affinity (Kd 19.28μM) towards HbA as compared to other drugs, selenomethionine, selenocystine and methylseleninic acid (Kd 7.69μM, 4.88μM and 10.5μM at 37°C respectively). This result is also supported by the molecular docking study. Methylseleninic acid was found to have detrimental effects on nitrite induced methemoglobinemia, a hematological disorder caused due to excessive conversion of Fe2+ to Fe3+ in hemoglobin. Hence the results of the study would help to develop a better insight on the mechanism of action and anticipate the toxicity of these drugs which require further optimization before their actual use in the treatment of cancer.

Optimization of nitrate and selenate reduction in an ethanol-fed fluidized bed reactor via redox potential feedback control

Electron donors are a major cost-factor in biological removal of oxyanions, such as nitrate and selenate from wastewater. In this study, an online ethanol dosing strategy based on feedback control of oxidation-reduction potential (ORP) was designed to optimize the performance of a lab-scale fluidized bed reactor (FBR) in treating selenate and nitrate (5 mM each) containing wastewater. The FBR performance was evaluated at various ORP setpoints ranging between −520 mV and −240 mV (vs. Ag/AgCl). Results suggested that both nitrate and selenate were completely removed at ORPs between −520 mV and −360 mV, with methylseleninic acid, selenocyanate, selenosulfate and ammonia being produced at low ORPs between −520 mV and −480 mV, likely due to overdosing of ethanol. At ORPs between −300 mV and −240 mV, limited ethanol dosing resulted in an apparent decline in selenate removal whereas nitrate removal remained stable. Resuming the ORP to −520 mV successfully restored complete selenate reduction. An optimal ORP of −400 mV was identified for the FBR, whereby selenate and nitrate were nearly completely removed with a minimal ethanol consumption. Overall, controlling ORP via feedback-dosing of the electron donor was an effective strategy to optimize FBR performance for reducing selenate and nitrate in wastewater.

Expression of ER-resident selenoproteins and activation of cancer cells apoptosis mechanisms under ER-stress conditions caused by methylseleninic acid.

The aim of this work was to study changes in gene expression levels of 7 ER-resident selenoproteins under ER-stress caused by the action of a selenium-containing compound of organic nature, methylselenic acid using three human cancer cell lines DU 145 (prostate carcinoma), MCF 7 (breast adenocarcinoma)and HT-1080 (fibrosarcoma). According to the obtained results, we can speak of a synchronous changes in the expression of SELT and SEP15 mRNA depending on the concentration of MSA for 24h, while the pattern of SELM expression was completely opposite and was radically different from other selenoproteins. It should be noted that in HT-1080 cells, the expression pattern of SELM differed from the expression pattern in two other cancer cells, while the expression patterns of other ER-resident selenoproteins (SELT, SEP15, SELK, SELS, SELN and DIO2) differed slightly depending on the cell line. Also we investigated the molecular mechanisms of UPR caused by MSA-induced ER stress in three cancer cell lines. According to the obtained results, it can be assumed that in DU 145 cells, MSA promotes activation of the PERK signaling pathway of UPR. In fibrosarcoma cells MSA was promoted the activation of ATF-6 UPR signaling pathway. In MCF 7 cells, MSA promoted the activation of two pro-apoptotic UPR signaling pathways at once: IRE1 and ATF-6.The results of this work once again demonstrate that the mechanisms of ER-stress regulation caused by the same agent, in this case, MSA, lead to the activation of different UPR signaling pathways in different cancer cells, and about their relationship.

Optimizing Mixtures of Se Compounds as Adjuvants to Therapeutic Agents

Abstract Objectives Different chemical forms of selenium (Se) regulate distinct sets of genes and have different metabolic effects. We previously showed that mixtures of different Se compounds can have greater inhibitory effects on prostate cancer cell viability than individual chemical forms. Further, we showed that blends of different Se forms can be optimized using response surface methodology. Previous investigators showed that single forms of Se can potentiate the effects of chemotherapeutic and other agents. We hypothesized that optimized mixtures of different forms of Se would be more effective than individual Se compounds in enhancing the efficacy of Se-drug combinations. Our objective was to provide proof of principle for this hypothesis. Methods Response surface methodology was used to optimize a blend of methylseleninic acid (MSA), selenite (SEL) and Nano Se to achieve maximum reduction of cell viability in LNCaP prostate cancer cells. Apalutamide (APA), Enzalutamide (ENZ), Docetaxel (DOC), and Mitoxantrone (MIT) were each combined with a single Se compound, or with the optimized blend. Cell viability assays were done using Alamar Blue. Results The optimized mix of Se forms, determined using response surface methodology, was a 50:50 blend of MSA and SEL, that surprisingly did not include Nano Se. All medium supplemented with Se compounds contained 10 μM Se. MIT treatment alone reduced cell viability &amp;gt;90% and showed no further reductions due to added Se. Addition of either form of Se to APA, DOC, or ENZ significantly decreased cell viability compared to treatment with the drug alone (P values: 0.008 - 0.041). Similarly, in 5 out of 6 cases, combination of the optimized blend of Se compounds with the drug resulted in further decreases in cell viability, compared to the mix of drug plus one chemical form of Se (P values: 0.013 – &amp;lt; 0.001). Conclusions These results provide proof of principle that the substitution of an optimized blend of Se compounds for a single Se form, may increase the efficacy of previously reported drug-Se combinations and treatments. Optimization of blends of different Se compounds can be done under conditions customized to their intended use to achieve a desired outcome. Funding Sources This work was funded by the BYU Simmons Center for Cancer Research.

Activation of Signal Pathways of Apoptosis under Conditions of Prolonged ER-Stress Caused by Exposure of Mouse Testicular Teratoma Cells to Selenium-Containing Compounds.

Aim to study the molecular mechanisms of apoptotic death of mouse testicular teratocarcinoma cells (line F-9) under exposure to the widely used selenium-containing compounds with antitumor activity, sodium selenite and methylseleninic acid. Methods fluorescence microscopy, MTT assay, Western blotting. Results It was shown that sodium selenite at a concentration of 10 μM and methylseleninic acid at concentrations of 1 and 10 μM cause apoptosis-dependent death of F-9 cells, excluding necrotic death. Western blotting showed an increase in the expression of XBP1s when treating F-9 cells with 1 μM methylseleninic acid. Conclusions 10 μM methylseleninic acid leads to cell apoptosis, most likely by activation of the IRE1 signaling pathway under prolonged stress of the endoplasmic reticulum.

Synergistic Combination of Sulforaphane and Methylseleninic Acid in Inhibiting the Proliferation of MCF-7 Breast Cancer Cells

Synergistic Combination of Sulforaphane and Methylseleninic Acid in Inhibiting the Proliferation of MCF-7 Breast Cancer Cells

The potential effect of methylseleninic acid (MSA) against γ-irradiation induced testicular damage in rats: Impact on JAK/STAT pathway

This study suggested that methylseleninic acid (MSA) could respond to the inflammatory signaling associated with ionizing radiation-induced testicular damage. Mature male rats were divided into four groups: negative control, whole body γ-irradiated (IRR) (5 Gy), MSA (0.5 mg/kg, daily for nine consecutive days), and MSA+ IRR groups. MSA increased serum testosterone level and testicular glutathione peroxidase (GPx) as well as decreased the percentage of sperm abnormalities. Radiation prompted inflammatory signaling in the testes through increasing phospho-janus kinase1 (p-JAK1), phospho-signal transducers and activators of transcription 3 (p-STAT3) protein expressions. This induced increment in the inflammatory markers including nuclear factor- kappa B (NF-κB) and interleukin-1beta (IL-1β) levels. Also, radiation induced elevation of nitric oxide (NO) and malondialdhyde (MDA) levels with consequent reduction in testicular reduced glutathione level (GSH) and superoxide dismutase (SOD) activity. MSA significantly counteracted the radiation effect on testicular nuclear factor erythroid-2-related factor-2 (Nrf2) and suppressor of cytokine signaling (Socs3) protein expressions. In summary, this investigation proposed that MSA preserved spermatogenesis through increasing testosterone levels and GPx activity. Additionally, it diminished testicular inflammation by increasing of Nrf2 and Socs3 levels leading to reducing of p-JAK1, p-STAT3 and NF-κB levels. Histopathological examination results of testicular tissues showed a coincidence with the biochemical analysis.

Protein-partners of selenoprotein SELM and the role of selenium compounds in regulation of its expression in human cancer cells

The search of potential partners of human SELM in lysates of two cancer cell lines HT-1080 (fibrosarcoma) and MCF-7 (breast adenocarcinoma) was carried out. Two cytoplasmic actin isoforms: cytoplasmic actin 1 (cytoskeleton b-actin) and cytoplasmic actin 2 (cytoskeletal g-actin) was identified as partners. In addition, the influence of two widely used antitumor selenium compounds (sodium selenite and methylseleninic acid) on the expression SELM in cancer cells was studied. According to the results obtained by real-time PCR and Western blotting, we was concluded that 1 µM and 10 µM sodium selenite was not affected on the expression SELM in fibrosarcoma cells, whereas in breast adenocarcinoma cells 1 µM sodium selenite slightly increased of expression and 10 µM resulted in a significant decrease (about 2 times). Methylseleninic acid in both cancer cell lines increased the expression of SELM gene, the most pronounced effect was observed when fibrosarcoma cells were treated with 10 µM MSC (increased expression of the hSelm gene by almost 4 times).

Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells.

The growth inhibitory efficacy of methylseleninic acid (MSA) in prostate cancer cells has been documented extensively. However, our understanding of the immediate targets that are key to the growth inhibitory effects of MSA remains limited. Here, using multiple preclinical prostate cancer models, we demonstrated in vitro and in vivo that GDF15 is a most highly induced, immediate target of MSA. We further showed that knockdown of GDF15 mitigates MSA inhibition of cell proliferation and induction of apoptosis. Analysis of gene expression data from over 1000 primary and 200 metastatic prostate cancer samples revealed that GDF15 expression is decreased in metastatic prostate cancers compared to primary tumors and that lower GDF15 levels in primary tumors are associated with higher Gleason scores and shorter survival of the patients. Additionally, pathways that are negatively correlated with GDF15 levels in clinical samples are also negatively correlated with MSA treatment in cultured cells. Since most, if not all, of these pathways have been implicated in prostate cancer progression, suppressing their activities by inducing GDF15 is consistent with the anticancer effects of MSA in prostate cancer. Overall, this study provides support for GDF15 as an immediate target of MSA in prostate cancer cells.

Protein Partners of Selenoprotein SELM and the Role of Selenium Compounds in Regulation of Its Expression in Human Cancer Cells.

The search for potential partners of human SELM in lysates of two cancer cell lines, HT-1080 (fibrosarcoma) and MCF-7 (breast adenocarcinoma), was carried out. Two cytoplasmic actin isoforms-cytoplasmic actin 1 (cytoskeleton β-actin) and cytoplasmic actin 2 (cytoskeletal γ-actin)-were identified as partners. In addition, the influence of two widely used antitumor selenium compounds (sodium selenite and methylseleninic acid) on the expression of SELM in cancer cells was studied. On the basis of the results obtained by real-time PCR and Western blotting, we concluded that 1 μM and 10 μM sodium selenite did not affect the expression of SELM in fibrosarcoma cells, whereas in breast adenocarcinoma cells 1 μM sodium selenite slightly increased expression and 10 μM sodium selenite significantly (approximately 2 times) decreased it. Methylseleninic acid in both cancer cell lines increased the SELM gene expression; the most pronounced effect was observed when fibrosarcoma cells were treated with 10 µM MSA (the expression of the hSelm gene increased almost 4 times).

Dietary Selenium Supplementation Does Not Attenuate Mammary Tumorigenesis-Mediated Bone Loss in Male MMTV-PyMT Mice.

Bone wasting occurs during the progression of breast cancer and contributes to breast cancer mortality. We evaluated the effect of methylseleninic acid (MSeA), an anti-carcinogenic form of selenium, on bone microstructural changes in the presence of mammary tumors in a male breast cancer model of mouse mammary tumor virus-polyomavirus middle T-antigen (MMTV-PyMT). In this study, we performed microcomputed tomographic analysis of femurs and vertebrae collected from a study showing that dietary supplementation with MSeA reduces mammary tumorigenesis in male mice. Compared to age-matched, non-tumor-bearing mice (MMTV-PyMT negative), the presence of mammary tumors significantly reduced the bone volume fraction, trabecular thickness, and bone mineral density while it increased the structure model index in femurs, but not in vertebrae. Moreover, mammary tumorigenesis decreased plasma concentrations of osteocalcin. Supplementation with MSeA did not affect these changes in MMTV-PyMT mice. In conclusion, mammary tumorigenesis caused bone loss in MMTV-PyMT mice. However, dietary supplementation with MSeA did not attenuate mammary tumor-associated bone loss in this model of male breast cancer.

Methylseleninic Acid Suppresses Breast Cancer Growth via the JAK2/STAT3 Pathway.

Previous studies show that methylseleninic acid (MSA), which is the most common selenium derivative used as a drug in humans, exerts specific cytotoxic effects in several cancer cell types. However, the complex mechanism of these effects has not been fully elucidated. Here, we demonstrate by Cell Counting Kit-8 in mouse breast cancer cell line 4T1 that MSA inhibits cell viability in a concentration-dependent (5, 10, 20 μmol/L) and time-dependent (6, 12, 24 hours) manner. Flow cytometry, Western blot, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analyses indicated that MSA inhibits cancer cell invasion and induces apoptosis by the activation of caspase-3, poly ADP ribose polymerase 1 (PARP1), and BCL2-associated X. Furthermore, MSA demonstrated anticancer activity by inhibiting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. The MSA treatment for 24 hours decreased the phosphorylation of JAK2 and STAT3 in 4T1 cells by Western blot. We also confirmed this with the use of a JAK2 chemical inhibitor, AG490, as a positive control. In a 4T1 orthotopic allograft model, morphological and TdT-mediated dUTP nick-end labeling analyses showed that MSA treatment (1.5 mg/kg/weight) for 28 days inhibits tumor growth consistent with the clinical anticancer drug cyclophosphamide. Our observations demonstrate that MSA is a potent anticancer drug in breast cancer and uncovered a key role of the JAK2/STAT3 pathway in modulating tumor growth.

Methylseleninic Acid Induces Lipid Peroxidation and Radiation Sensitivity in Head and Neck Cancer Cells.

Combination radiation and chemotherapy are commonly used to treat locoregionally advanced head and neck squamous cell carcinoma (HNSCC). Aggressive dosing of these therapies is significantly hampered by side effects due to normal tissue toxicity. Selenium represents an adjuvant that selectively sensitizes cancer cells to these treatments modalities, potentially by inducing lipid peroxidation (LPO). This study investigated whether one such selenium compound, methylseleninic acid (MSA), induces LPO and radiation sensitivity in HNSCC cells. Results from 4,4-difluoro-4-bora-3a,4a-diaza-S-indacene (BODIPY) C11 oxidation and ferric thiocyanate assays revealed that MSA induced LPO in cells rapidly and persistently. Propidium iodide (PI) exclusion assay found that MSA was more toxic to cancer cells than other related selenium compounds; this toxicity was abrogated by treatment with α-tocopherol, an LPO inhibitor. MSA exhibited no toxicity to normal fibroblasts at similar doses. MSA also sensitized HNSCC cells to radiation as determined by clonogenic assay. Intracellular glutathione in cancer cells was depleted following MSA treatment, and supplementation of the intracellular glutathione pool with N-acetylcysteine sensitized cells to MSA. The addition of MSA to a cell-free solution of glutathione resulted in an increase in oxygen consumption, which was abrogated by catalase, suggesting the formation of H2O2. Results from this study identify MSA as an inducer of LPO, and reveal its capability to sensitize HNSCC to radiation. MSA may represent a potent adjuvant to radiation therapy in HNSCC.

Methylseleninic Acid and Grape Seed Extract Alleviate Tamoxifen Induce Hepatotoxicity in Rats

Objective The current study aimed to evaluate the hepatoprotective potential of methylseleninic acid (MSA) and grape seed extract on tamoxifen-induce hepatotoxicity in female rats.

The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells.

Selenium, a trace element with anticancer properties, can reduce harmful toxicities of chemotherapy and radiotherapy without compromising efficacy. However, the dose-response relationship in normal versus malignant human cells is unclear. We evaluated how methylseleninic acid (MSA) modulates the toxicity and efficacy of chemotherapy and radiation on malignant and non-malignant human mononuclear blood cells in vitro. We specifically investigated its effects on endoplasmic reticulum stress induction, intracellular glutathione concentration, DNA damage and viability of peripheral blood mononuclear cells and THP1 monocytic leukaemia cells in response to radiation, cytosine arabinoside or doxorubicin chemotherapy. MSA, at lower concentrations, induced protective responses in normal cells but cytotoxic effects in malignant cells, alone and in conjunction with chemotherapy or radiation. However, in normal cells higher concentrations of MSA were directly toxic and increased the cytotoxicity of radiation but not chemotherapy. In malignant cells higher MSA concentrations were generally more effective in combination with cancer treatments. Thus, optimal MSA concentrations differed between normal and malignant cells and treatments. This work supports clinical reports that selenium can significantly reduce dose-limiting toxicities of anticancer therapies and potentially improve efficacy of anticancer treatments. The optimal selenium compound and dose is not yet determined.

Methylseleninic Acid Sensitizes Ovarian Cancer Cells to T-Cell Mediated Killing by Decreasing PDL1 and VEGF Levels.

Redox active selenium (Se) compounds at sub toxic doses act as pro-oxidants with cytotoxic effects on tumor cells and are promising future chemotherapeutic agents. However, little is known about how Se compounds affect immune cells in the tumor microenvironment. We demonstrate that the inorganic Se compound selenite and the organic methylseleninic acid (MSA) do not, despite their pro-oxidant function, influence the viability of immune cells, at doses that gives cytotoxic effects in ovarian cancer cell lines. Treatment of the ovarian cancer cell line A2780 with selenite and MSA increases NK cell mediated lysis, and enhances the cytolytic activity of T cells. Increased T cell function was observed after incubation of T cells in preconditioned media from tumor cells treated with MSA, an effect that was coupled to decreased levels of PDL1, HIF-1α, and VEGF. In conclusion, redox active selenium compounds do not kill or inactivate immune cells at doses required for anti-cancer treatment, and we demonstrate that MSA enhances T cell-mediated tumor cell killing via PDL1 and VEGF inhibition.

Novel Methylselenoesters Induce Programed Cell Death via Entosis in Pancreatic Cancer Cells.

Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds.

Abstract 270: Effect of dietary methylseleninic acid and Se-methylselenocysteine on carcinogen-induced, androgen-promoted prostate carcinogenesis in rats

Abstract Selenomethionine (SeMet) did not inhibit development of prostate cancer in the SELECT trial and in preclinical rat models. However, we and others have shown that oral intake of next-generation selenium (Se) forms, especially methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC), inhibits prostate carcinogenesis in the TRAMP mouse model and growth of human prostate cancer cells xenografted in immunodeficient mice. We recently showed that MSeA suppresses progression of high-grade prostatic intraepithelial neoplasia to adenocarcinoma in pten-deficient mice (Cancer Prev Res 2016;9:35-42). To determine whether next-generation Se forms inhibit prostate carcinogenesis in models driven by a different etiology, we tested the in vivo effect of different Se forms fed to rats undergoing chemically induced androgen-promoted prostate carcinogenesis. We previously established that SeMet was not inhibitory in this model (Cancer Prev Res 2010;3:381-92). Wistar-Unilever (WU) rats (10-12 wks) were sequentially treated with androgen receptor blocker flutamide for 21 days (10 mg/kg/day by gavage), followed by testosterone propionate (TP, 10 mg/kg, s.c) on day 22. Three days after TP, the carcinogen methylnitrosourea (MNU, 30 mg/kg/bw) was administered by i.p. injection. One week later, the rats received slow-release Silastic implants containing testosterone. Rats were then randomized to one of three groups fed the AIN-93M diet supplemented with 3 ppm of Se as MSeA or MSeC or control AIN-93M diet. Moribund animals were euthanized and the study was terminated 400 days after MNU injection. Mean survival (days ± SEM) after MNU was 344±11 in controls (n=31), 354±8 in MSeA fed rats (n=30), and 363±10 in rats given MSeC (n=29). These differences were not statistically significant, which was confirmed by survival analysis using the logrank test. Overall tumor incidence in all accessory sex glands combined (dorsolateral and anterior prostate plus seminal vesicle) was 68% in controls, 83% in MSeA rats, and 72% in MSeC rats. The incidence of large tumors of uncertain origin was 42% in controls, 40% in MSeA rats, and 41% in MSeC rats. The incidence of smaller tumors clearly confined to dorsolateral and/or anterior prostate was 19% in controls, 20% in MSeA rats, and 38% in MSeC rats (some rats had more than one tumor). None of these differences was statistically significant and there were no shifts from large to small tumor or small to large tumors. Thus, MSeA and MSeC were not preventive in this rat prostate carcinogenesis model. The contrast with the inhibitory effects of MSeA in the TRAMP and pten-deficient mouse models may be due to differences in administered dose or fundamental rat-mouse differences in Se metabolism that impact chemoprevention by Se compounds. Supported by NIH grant CA172169. Citation Format: Maarten C. Bosland, Michael J. Schlicht, Yibin Deng, Junxuan Lu. Effect of dietary methylseleninic acid and Se-methylselenocysteine on carcinogen-induced, androgen-promoted prostate carcinogenesis in rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 270.