Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2014-12-01T11:55:38Z No. of bitstreams: 2 Dissertação - Bruna dos Santos Rodrigues - 2013.pdf: 1797836 bytes, checksum: b56e1b3bdd63eeb9040d2ef050f157f8 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-12-04T14:18:47Z (GMT) No. of bitstreams: 2 Dissertação - Bruna dos Santos Rodrigues - 2013.pdf: 1797836 bytes, checksum: b56e1b3bdd63eeb9040d2ef050f157f8 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-12-04T14:18:47Z (GMT). No. of bitstreams: 2 Dissertação - Bruna dos Santos Rodrigues - 2013.pdf: 1797836 bytes, checksum: b56e1b3bdd63eeb9040d2ef050f157f8 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-08-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The death mechanisms induced by a new synthetic compound (4-FTC) in adenocarcinoma prostate cells (PC-3) and its toxicity were investigated in this study. PC-3 cells cytotoxity was evaluated by MTT reduction assay. The mechanisms involved in PC-3 death and cell cycle were investigated by flow cytometry and colorimetric assays. The compound toxicity was analized by cytotoxicity of mononuclear cells (MTT reduction assay) and 3T3 cells (neutral red uptake assay), myelotoxicity, haemolytic activity and acute oral toxicity. 4-FTC has concentration dependent cytotoxic activity in PC-3 cells, and 184,6 μM IC50. Investigation of death mechanisms indicated death by apoptosis, because of the significant increase in phosphatidylserine externalization (109,83%), loss of mytochondrial membrane potential (41,96%), significant increase of DNA fragmentation (284,02%) and capases 3/7 and 9 activity increase, 13,12% and 12,8%, respectively. Furthermore, the treatment of PC-3 cells wih 4-FTC did not induce the reactive oxygen species production, as well as, the induction of acid autophagic vesicles generation and did not change the cell cycle significantly. Althought 4-FTC was able to modulate the expression of some proteins that regulate cell cycle, incresead the expression of p53, p21 and p27. Thus, the results suggests that 4-FTC induced PC-3 death by apoptosis dependent by mitochondrial pathway activation. In toxicity evaluation, 4-FTC presented 52,86 μM and 19,63 μM IC50 to mononuclear and 3T3 cells, respectively; 27,35 μM IC50 to hematopoietic precursors; low acute oral toxicity, classified in GHS category 5, and not significant haemolytic activity. / Neste trabalho, investigaram-se os mecanismos de morte induzidos por um novo composto sintético, 4-fluorbenzaldeidotiossemicarbazona (4-FTC), nas células de adenocarcinoma prostático PC-3 e alguns parâmetros da toxicidade desse composto. A citotoxicidade nas células PC-3 foi avaliada pelo método de redução do MTT, método colorimétrico para avaliar a viabilidade celular. A investigação dos mecanismos de morte induzidos foi realizada por citometria de fluxo e ensaio colorimétrico. A toxicidade do composto foi avaliada pela citotoxicidade em células mononucleares pelo método de redução do MTT, citotoxicidade em células 3T3 pelo método de incorporação do vermelho neutro, mielotoxicidade, potencial hemolítico e toxicidade oral aguda. Os resultados obtidos mostram atividade citotóxica concentração dependente, com CI50 de 184,6 μM para PC-3. A investigação dos mecanismos de morte induzidos indicou morte por apoptose, pois houve aumento significativo da externalização da fosfatidilsserina (109,83%), perda do potencial de membrana mitocondrial em 41,96%, aumento significativo da fragmentação de DNA (284,02%) e aumento de caspases 3/7 e 9, em 13,12% e 12,8%, respectivamente. Além disso, não induziu a produção de espécies reativas de oxigênio, bem como, a formação de vesículas autofágicas ácidas e não alterou o perfil do ciclo celular de forma significativa. Embora tenha modulado a expressão de proteínas reguladoras do ciclo celular, aumentando a expressão de p53, p21 e p27. Assim, pode-se sugeririr que o 4-FTC induz morte por apoptose por meio de mecanismos de ativação dependentes da via mitocondrial em células PC-3. Na avaliação da toxicidade, o 4-FTC apresentou concentração inibitória 50% (CI50) de 52,86 μM e 19,63 μM para células mononuclerares e células 3T3, respectivamente; CI50 de 27,35 μM para precursores hematopoiéticos; baixa toxicidade oral aguda, sendo classificado na categoria 5 e baixo potencial hemolítico.

Devido ao grande avanço na descoberta de novos fármacos a partir de compostos naturais, tornou-se interessante avaliar o potencial antiproliferativo de moléculas isoladas de extratos de plantas. Este trabalho prioriza o estudo da atividade antitumoral de benzofenonas (carifenona A e carifenona B) e floroglucionóis (japonicina A e uliginosina B), isolados das espécies nativas do sul do Brasil, Hypericum carinatum e Hypericum myrianthum, respectivamente, bem como a associação destes com quimioterápicos utilizados na clínica. Os experimentos propostos foram realizados em modelos in vitro, utilizando diferentes tipos de linhagens tumorais humanas comercialmente disponíveis. Foi avaliado o efeito de diferentes doses destes compostos através de experimentos de viabilidade e sobrevivência celular, análise morfométrica nuclear (NMA) e citometria de fluxo. Na análise estatística foi utilizada a variância de uma via (ANOVA) seguida de teste post-hoc (Tukey). Os resultados foram expressos como média ± erro padrão da média (SEM), sendo valores de P menores do que 0,05 considerados significativos. Verificamos que nas linhagens de adenocarcinoma de ovário e colorretal e de glioblastoma (OVCAR-3, HT-29 e U-251) ocorreu uma diminuição significativa na viabilidade celular quando tratadas com a dose de 100μg/mL tanto de carifenona A como de carifenona B, enquanto os compostos japonicina A (50μg/mL) e uliginosina B (20μg/mL) só foram ativos na linhagem OVCAR-3. Dentre as associações com quimioterápicos, a única que apresentou efeito sinérgico foi a combinação de japonicina A e paclitaxel na linhagem OVCAR-3. A partir deste momento selecionamos a japoncina A para dar continuidade aos estudos. Este composto foi avaliado frente a outros tipos de linhagens tumorais, sendo ativa somente em células de adenocarcinoma de ovário e próstata (OVCAR-3 e PC-3). Na linhagem PC-3, a análise do ciclo celular demonstrou decréscimo da fase G1 e indução ao arraste da fase G2, assim como, através da técnica de NMA, foi verificado um aumento de células apoptóticas, quando as células foram tratadas com japonicina A. Estudos moleculares devem ser realizados para melhor entendimento do mecanismo de ação da japonicina A, composto que pode servir de modelo para o desenho de fármacos mais específicos para este tipo de neoplasia. / Due to the great progress in the discovery of new drugs from natural compounds, it has become interesting to evaluate the antiproliferative activity of molecules isolated from plant extracts. This work emphasizes the study of antitumor activity of benzophenones (cariphenone A and cariphenone B) and phloroglucionols (japonicin A and uliginosin B), isolated from Hypericum species native to southern Brazil, H. carinatum and H. myrianthum, respectively, as well as their association with chemotherapeutic drugs used in the clinic. The proposed experiments were performed in vitro using commercially available cell lines. The effect of different doses of these compounds were evaluated via cell viability and survival assay, nuclear morphometric analysis (NMA) and flow cytometry. One way analysis of variance (ANOVA) followed by post hoc tests (Tukey) were utilized for statistical analysis. Results were expressed as mean ± standard error of the mean (SEM), and P values less than 0.05 were considered significant. We found that in ovarian, colorectal (adenocarcinoma) and glioblastoma cell lines (OVCAR-3, HT-29 and U-251) a significant decrease in cell viability occurred when these were treated with a dose of 100μg/mL of cariphenone A and B, while compounds japonicin A (50μg/mL) and uliginosin B (20μg/mL) were active only in OVCAR- 3. Among the associations with chemotherapeutic agents, only japonicin A presented a synergistic effect with paclitaxel in the OVCAR-3 cell line. We then selected japonicin A for evaluation against other cell lines, but its effects were only observed in ovary and prostate adenocarcinoma cell lines (OVCAR-3 e PC-3). In PC-3, the cell cycle revealed a decreased in the G1 phase and induction of G2 arrest, the NMA showed an increase in apoptotic cells when cells were treated with japonicin A. More studies should be conducted to better understand the mechanisms of action of japonicin A, since this compound may serve as pharmacophore model for the design of more specific drugs to treat this tumor type.

v anglickom jazyku Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: František Lach Supervisor: Mgr. Pavel Bárta, PhD Consultant: Mgr. Lucie Hyršová Title of diploma thesis: In vitro saturation study of 99m Tc-HYNIC-ramucirumab on PC-3 cell line The number of malignant tumours in the population has increased in recent years. Due to the frequent serious sides effects of chemotherapeutic drugs on the whole organism, targeted antitumor therapy is at the forefront. Due to its specific effect on the regulatory and signal pathways of protein structures, monoclonal antibodies are used for the target anti-tumour therapy. The basic properties of the growing tumour include vasculogenesis (the ability to build new blood vessels from the endothelial precursors) and angiogenesis (the process of self-inducing formation of blood vessels). Endothelial tumour progenitors include vascular endothelial growth factor (VEGF). VEGF activates its biological activity by binding to its transmembrane tyrosine-kinase receptors VEGFR. Indeed, the inhibition of the vascular endothelial factor receptors is the target of some monoclonal antibodies. Ramucirumab is a monoclonal antibody that selectively inhibits VEGF receptor type 2 (VEGFR-2) and thereby...

Devido ao grande avanço na descoberta de novos fármacos a partir de compostos naturais, tornou-se interessante avaliar o potencial antiproliferativo de moléculas isoladas de extratos de plantas. Este trabalho prioriza o estudo da atividade antitumoral de benzofenonas (carifenona A e carifenona B) e floroglucionóis (japonicina A e uliginosina B), isolados das espécies nativas do sul do Brasil, Hypericum carinatum e Hypericum myrianthum, respectivamente, bem como a associação destes com quimioterápicos utilizados na clínica. Os experimentos propostos foram realizados em modelos in vitro, utilizando diferentes tipos de linhagens tumorais humanas comercialmente disponíveis. Foi avaliado o efeito de diferentes doses destes compostos através de experimentos de viabilidade e sobrevivência celular, análise morfométrica nuclear (NMA) e citometria de fluxo. Na análise estatística foi utilizada a variância de uma via (ANOVA) seguida de teste post-hoc (Tukey). Os resultados foram expressos como média ± erro padrão da média (SEM), sendo valores de P menores do que 0,05 considerados significativos. Verificamos que nas linhagens de adenocarcinoma de ovário e colorretal e de glioblastoma (OVCAR-3, HT-29 e U-251) ocorreu uma diminuição significativa na viabilidade celular quando tratadas com a dose de 100μg/mL tanto de carifenona A como de carifenona B, enquanto os compostos japonicina A (50μg/mL) e uliginosina B (20μg/mL) só foram ativos na linhagem OVCAR-3. Dentre as associações com quimioterápicos, a única que apresentou efeito sinérgico foi a combinação de japonicina A e paclitaxel na linhagem OVCAR-3. A partir deste momento selecionamos a japoncina A para dar continuidade aos estudos. Este composto foi avaliado frente a outros tipos de linhagens tumorais, sendo ativa somente em células de adenocarcinoma de ovário e próstata (OVCAR-3 e PC-3). Na linhagem PC-3, a análise do ciclo celular demonstrou decréscimo da fase G1 e indução ao arraste da fase G2, assim como, através da técnica de NMA, foi verificado um aumento de células apoptóticas, quando as células foram tratadas com japonicina A. Estudos moleculares devem ser realizados para melhor entendimento do mecanismo de ação da japonicina A, composto que pode servir de modelo para o desenho de fármacos mais específicos para este tipo de neoplasia. / Due to the great progress in the discovery of new drugs from natural compounds, it has become interesting to evaluate the antiproliferative activity of molecules isolated from plant extracts. This work emphasizes the study of antitumor activity of benzophenones (cariphenone A and cariphenone B) and phloroglucionols (japonicin A and uliginosin B), isolated from Hypericum species native to southern Brazil, H. carinatum and H. myrianthum, respectively, as well as their association with chemotherapeutic drugs used in the clinic. The proposed experiments were performed in vitro using commercially available cell lines. The effect of different doses of these compounds were evaluated via cell viability and survival assay, nuclear morphometric analysis (NMA) and flow cytometry. One way analysis of variance (ANOVA) followed by post hoc tests (Tukey) were utilized for statistical analysis. Results were expressed as mean ± standard error of the mean (SEM), and P values less than 0.05 were considered significant. We found that in ovarian, colorectal (adenocarcinoma) and glioblastoma cell lines (OVCAR-3, HT-29 and U-251) a significant decrease in cell viability occurred when these were treated with a dose of 100μg/mL of cariphenone A and B, while compounds japonicin A (50μg/mL) and uliginosin B (20μg/mL) were active only in OVCAR- 3. Among the associations with chemotherapeutic agents, only japonicin A presented a synergistic effect with paclitaxel in the OVCAR-3 cell line. We then selected japonicin A for evaluation against other cell lines, but its effects were only observed in ovary and prostate adenocarcinoma cell lines (OVCAR-3 e PC-3). In PC-3, the cell cycle revealed a decreased in the G1 phase and induction of G2 arrest, the NMA showed an increase in apoptotic cells when cells were treated with japonicin A. More studies should be conducted to better understand the mechanisms of action of japonicin A, since this compound may serve as pharmacophore model for the design of more specific drugs to treat this tumor type.

Devido ao grande avanço na descoberta de novos fármacos a partir de compostos naturais, tornou-se interessante avaliar o potencial antiproliferativo de moléculas isoladas de extratos de plantas. Este trabalho prioriza o estudo da atividade antitumoral de benzofenonas (carifenona A e carifenona B) e floroglucionóis (japonicina A e uliginosina B), isolados das espécies nativas do sul do Brasil, Hypericum carinatum e Hypericum myrianthum, respectivamente, bem como a associação destes com quimioterápicos utilizados na clínica. Os experimentos propostos foram realizados em modelos in vitro, utilizando diferentes tipos de linhagens tumorais humanas comercialmente disponíveis. Foi avaliado o efeito de diferentes doses destes compostos através de experimentos de viabilidade e sobrevivência celular, análise morfométrica nuclear (NMA) e citometria de fluxo. Na análise estatística foi utilizada a variância de uma via (ANOVA) seguida de teste post-hoc (Tukey). Os resultados foram expressos como média ± erro padrão da média (SEM), sendo valores de P menores do que 0,05 considerados significativos. Verificamos que nas linhagens de adenocarcinoma de ovário e colorretal e de glioblastoma (OVCAR-3, HT-29 e U-251) ocorreu uma diminuição significativa na viabilidade celular quando tratadas com a dose de 100μg/mL tanto de carifenona A como de carifenona B, enquanto os compostos japonicina A (50μg/mL) e uliginosina B (20μg/mL) só foram ativos na linhagem OVCAR-3. Dentre as associações com quimioterápicos, a única que apresentou efeito sinérgico foi a combinação de japonicina A e paclitaxel na linhagem OVCAR-3. A partir deste momento selecionamos a japoncina A para dar continuidade aos estudos. Este composto foi avaliado frente a outros tipos de linhagens tumorais, sendo ativa somente em células de adenocarcinoma de ovário e próstata (OVCAR-3 e PC-3). Na linhagem PC-3, a análise do ciclo celular demonstrou decréscimo da fase G1 e indução ao arraste da fase G2, assim como, através da técnica de NMA, foi verificado um aumento de células apoptóticas, quando as células foram tratadas com japonicina A. Estudos moleculares devem ser realizados para melhor entendimento do mecanismo de ação da japonicina A, composto que pode servir de modelo para o desenho de fármacos mais específicos para este tipo de neoplasia. / Due to the great progress in the discovery of new drugs from natural compounds, it has become interesting to evaluate the antiproliferative activity of molecules isolated from plant extracts. This work emphasizes the study of antitumor activity of benzophenones (cariphenone A and cariphenone B) and phloroglucionols (japonicin A and uliginosin B), isolated from Hypericum species native to southern Brazil, H. carinatum and H. myrianthum, respectively, as well as their association with chemotherapeutic drugs used in the clinic. The proposed experiments were performed in vitro using commercially available cell lines. The effect of different doses of these compounds were evaluated via cell viability and survival assay, nuclear morphometric analysis (NMA) and flow cytometry. One way analysis of variance (ANOVA) followed by post hoc tests (Tukey) were utilized for statistical analysis. Results were expressed as mean ± standard error of the mean (SEM), and P values less than 0.05 were considered significant. We found that in ovarian, colorectal (adenocarcinoma) and glioblastoma cell lines (OVCAR-3, HT-29 and U-251) a significant decrease in cell viability occurred when these were treated with a dose of 100μg/mL of cariphenone A and B, while compounds japonicin A (50μg/mL) and uliginosin B (20μg/mL) were active only in OVCAR- 3. Among the associations with chemotherapeutic agents, only japonicin A presented a synergistic effect with paclitaxel in the OVCAR-3 cell line. We then selected japonicin A for evaluation against other cell lines, but its effects were only observed in ovary and prostate adenocarcinoma cell lines (OVCAR-3 e PC-3). In PC-3, the cell cycle revealed a decreased in the G1 phase and induction of G2 arrest, the NMA showed an increase in apoptotic cells when cells were treated with japonicin A. More studies should be conducted to better understand the mechanisms of action of japonicin A, since this compound may serve as pharmacophore model for the design of more specific drugs to treat this tumor type.

The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this mainly through a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. Another major way in which 1,25(OH)2D3 inhibits cell growth in prostate cancer is via membrane-initiated steroid signalling, which triggers activation of signal cascades upon steroid binding to a receptor complex, leading to induction of genes regulating cell growth, proliferation and apoptosis. The main prostate cancer inhibiting membrane-initiated route is the TGFβ signalling pathway, elicited by the protein TGFβ. Two other important proteins downstream in this cascade are Smad2 and Smad3. In this study the early effects of 1,25(OH)2D3 on activated Smad2/3 levelsin PC-3 prostate cancer cells were examined. PC-3 cells were incubated for 3, 5, 10, 30 and 60 minutes as well as 38 hours both together with 1,25(OH)2D3 of the concentrations 10-10 and 10-7 M and without. Western Blots were then performed on supernatants from the cells treated followed by treatment of the membranes with primary antibodies against phosphorylated Smad2/3 C-terminal linker regions, alkaline phosphatase conjugated secondary antibodies and finally visualization with BCIP/ NBT tablets. As the downstream cascade protein JNK is a proposed activator of Smad2/3, this procedure was also repeated with a JNK inhibitor. This is a follow-up to an earlier study which examined the influence of 1,25(OH)2D3 on TGFβ levels using the same doses and time points and which found that 1,25(OH)2D3 initially lowered the level of active TGFβ, then increased it. The results of this study indicated a 1,25(OH)2D3 mediated induction of the same pattern in the levels of active Smad2 and 3, both with and without JNK inhibitor. The results did not indicate that 1,25(OH)2D3 activates the Smad2/3 C-terminal linker region via the JNK pathway.

The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this mainly through a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. Another major way inwhich 1,25(OH)2D3 inhibits cell growth in prostate cancer is via membrane-initiated steroid signalling, which triggers activation of signal cascades upon steroid binding to a receptor complex, leading to induction of genes regulating cell growth, proliferation and apoptosis. The main prostate cancer inhibiting membrane-initiated route is the TGFβ signalling pathway, elicited by the protein TGFβ. Another important protein downstream in this cascade is Smad2. In this study the early effects of 1,25(OH)2D3 on activated Smad2 levels in PC-3 prostate cancer cells were examined. PC-3 cells were incubated for 5, 10, 30 and 60 minutes as well as 24 and 40 hours both together with 1,25(OH)2D3 of the concentrations 10-10 and 107 M and without. An ELISA assay scanning for activated Smad2 was then performed on supernatants from both treated and untreated cells. This is a follow-up to an earlier study which examined the influence of 1,25(OH)2D3 on TGFβ levels using the same doses and similar time points and which found that 1,25(OH)2D3 initially lowered the level of active TGFβ, then increased it. The results of this study showed a statistically insignificant, time delayed 1,25(OH)2D3 mediated induction of the same pattern in the levels of active Smad2. / Project Work in Biomedicine, Advanced Level, 7.5 ECTS

<p>The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this mainly through a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. Another major way in which 1,25(OH)2D3 inhibits cell growth in prostate cancer is via membrane-initiated steroid signalling, which triggers activation of signal cascades upon steroid binding to a receptor complex, leading to induction of genes regulating cell growth, proliferation and apoptosis. The main prostate cancer inhibiting membrane-initiated route is the TGFβ signalling pathway, elicited by the protein TGFβ. Two other important proteins downstream in this cascade are Smad2 and Smad3. In this study the early effects of 1,25(OH)2D3 on activated Smad2/3 levelsin PC-3 prostate cancer cells were examined. PC-3 cells were incubated for 3, 5, 10, 30 and 60 minutes as well as 38 hours both together with 1,25(OH)2D3 of the concentrations 10-10 and 10-7 M and without. Western Blots were then performed on supernatants from the cells treated followed by treatment of the membranes with primary antibodies against phosphorylated Smad2/3 C-terminal linker regions, alkaline phosphatase conjugated secondary antibodies and finally visualization with BCIP/ NBT tablets. As the downstream cascade protein JNK is a proposed activator of Smad2/3, this procedure was also repeated with a JNK inhibitor. This is a follow-up to an earlier study which examined the influence of 1,25(OH)2D3 on TGFβ levels using the same doses and time points and which found that 1,25(OH)2D3 initially lowered the level of active TGFβ, then increased it. The results of this study indicated a 1,25(OH)2D3 mediated induction of the same pattern in the levels of active Smad2 and 3, both with and without JNK inhibitor. The results did not indicate that 1,25(OH)2D3 activates the Smad2/3 C-terminal linker region via the JNK pathway.</p>

<p>The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this mainly through a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. Another major way inwhich 1,25(OH)2D3 inhibits cell growth in prostate cancer is via membrane-initiated steroid signalling, which triggers activation of signal cascades upon steroid binding to a receptor complex, leading to induction of genes regulating cell growth, proliferation and apoptosis. The main prostate cancer inhibiting membrane-initiated route is the TGFβ signalling pathway, elicited by the protein TGFβ. Another important protein downstream in this cascade is Smad2. In this study the early effects of 1,25(OH)2D3 on activated Smad2 levels in PC-3 prostate cancer cells were examined. PC-3 cells were incubated for 5, 10, 30 and 60 minutes as well as 24 and 40 hours both together with 1,25(OH)2D3 of the concentrations 10-10 and 107 M and without. An ELISA assay scanning for activated Smad2 was then performed on supernatants from both treated and untreated cells. This is a follow-up to an earlier study which examined the influence of 1,25(OH)2D3 on TGFβ levels using the same doses and similar time points and which found that 1,25(OH)2D3 initially lowered the level of active TGFβ, then increased it. The results of this study showed a statistically insignificant, time delayed 1,25(OH)2D3 mediated induction of the same pattern in the levels of active Smad2.</p> / Project Work in Biomedicine, Advanced Level, 7.5 ECTS

This research, focusing mainly on tocotrienols, includes two parts. The first part concerns the uptake and growth inhibition of tocotrienols in PC-3 cells. The second part is a study of the physiochemical properties of Vitamin E. In the cellular study our results suggested that position 5 of chroman head and side-chain are very important in determining the uptake of tocotrienols and growth inhibition of PC-3 cells. The uptake and growth inhibition are not necessarily related to the antioxidant properties of tocotrienols. Of the physiochemical studies, the results suggested that the antioxidant properties of vitamin E are due to the phenolic O-H group. In ethanol solution, each tocotrienol has a higher oxidation potential than its corresponding tocopherol. The oxidation potentials of vitamin E are in the order ofα-form < γform < δ-form. The theoretical calculations show that the side chains of tocotrienols are less ordered than those of tocopherols.