The α -Tomatine Exhibits Antiproliferative Activity, Rupture of Cell Membranes and Induces the Expression of APC Gene in the Human Colorectal Adenocarcinoma Cell Line (Ht-29)

Abstract The α-tomatine is a steroidal glycoalkaloid found in immature tomatoes (Lycopersicon esculentum) that has important biological functions including the inhibition of cancer cell growth and preventing metastasis. This study aimed to evaluate the effects of α-tomatine on cytotoxicity, cellular proliferation, apoptosis, and mRNA expression of APC, CCNA2, β-catenin, CASP9, BAK, BAX and BCL-XL in colorectal adenocarcinoma cell line HT-29. HT29 cells were treated with three concentrations of α-tomatine (0.1, 1 and 10 µg/mL), although only the 1 µg/mL concentration of α-tomatine was used to evaluate genetic expression patterns by real time-PCR. Results showed that α-tomatine was cytotoxic only at the 10 µg/mL concentration. Cell proliferation was significantly inhibited after the first 24 hours of treatment only with concentrations of 10 µg/mL. In contrast, there were no significant differences in apoptosis for any treatment. In the gene expression studies, only APC expression was significantly altered by α-tomatine treatment. In conclusion, α-tomatine has antiproliferative activity in the first 24h of treatment, does not induce apoptosis in this cell line and causes disruption of cell membranes, thereby increasing the expression of APC gene related to cell cycle.

Brown Flaxseed Prevents DNA Damage Induced by 1,2-Dimethylhydrazine in a Pre-Clinical Model

ABSTRACT The study evaluated the effects of brown flaxseed supplementation in natura on the prevention of DNA damage induced by 1,2-dimethylhydrazine (DMH) in vivo. The experimental groups were Negative and Positive Controls and the protocols of Pre-treatment, Simultaneous, Post-treatment, Pre+continuous in relation to the supplementation of brown flaxseed and administration with carcinogenic compound. The results showed that brown flaxseed supplementation does not cause genomic and genetic damage. In addition, brown flaxseed showed a chemopreventive food that reduced the damages assessed by the comet assay up to 94.07x and the damages assessed by the micronucleus assay up to 91.88x. Brown flaxseed supplementation also increased the frequency of monocytes and lymphocytes indicating immunological improvements. Thus, brown flaxseed supplementation is considered safe and reduces the frequency of DNA damage that can lead to tumors. Therefore, if these events are confirmed in humans, flaxseed will have reinforced its indication as a functional chemopreventive food in the prevention of cancer.

Chemopreventive activity of phenylalanine against damage mutagenic prompted by the acute administration of cyclophosphamide in pregnant and non-pregnant mice using the micronucleus test / Atividade quimiopreventiva da fenilalanina contra danos mutagênicos pela administração aguda de ciclofosfamida em ratas grávidas e não grávidas, utilizando o teste do micronúcleo

This study aimed to evaluate the quimiopreventive ability of phenylalanine. We used pregnant and non-pregnant female mice divided into the following groups: G1-PBS, (0.1 mL/kg b.w); G2, cyclophosphamide (35 mg/kg p.c.-i.p.); G3 and G4, phenylalanine (150 and 300 mg/kg b.w respectively-v.o.) and G5 and G6, association between the two doses of phenylalanine and cyclophosphamide, respectively. The peripheral blood samples were taken at T0, before the administration of any drug test and / or vehicles, also at T24 and T48 where the collections were made 24 and 48 h after administration of cyclophosphamide, respectively. A general analysis has found that, for the group of non-pregnant female, the antimutagenic evaluation showed reduction percentages of damage of 57.24 percent and 31.64 percent for G5 and G6, respectively, at T24, and 29.32 percent and 24.13 percent for G5 and G6, respectively, at T48. Antimutagenic pregnant animals in the 24 h quimiopreventive efficiency shown only for the lower dose (G5) and the percentages of reduction were 43.25 percent in G5 and G6 at 18.47 percent. At T48 the harm-reduction percentages were 44.67 percent and 37.76 percent for G5 and G6, respectively.

A presente pesquisa teve por objetivo avaliar a capacidade quimiopreventiva da fenilalanina. Utilizou-se um lote de fêmeas prenhes e não prenhes divididas nos seguintes grupos experimentais: G1, PBS (0,1 mL/kg p.c.); G2, ciclofosfamida (35 mg/kg p.c.-i.p.); G3, fenilalanina (150 mg/kg p.c.-v.o.) e G4, fenilalanina (300 mg/kg p.c.-v.o.) e G5 (150 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida); G6, (300 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida). As coletas de sangue periférico foram realizadas em T0, antes da administração de qualquer substância teste e/ou veículos, e igualmente em T24 e T48, onde as coletas foram realizadas respectivamente 24 e 48 h após a administração da ciclofosfamida. Em uma análise geral verificou-se que, para o grupo de fêmeas não prenhes, a avaliação da antimutagenicidade demonstrou porcentagens de redução de danos de 57,24 por cento e 31,64 por cento para G5 e G6, respectivamente, em T24, e 29,32 por cento e 24,13 por cento para G5 e G6, respectivamente, em T48. Nos animais prenhes a antimutagenicidade de 24 h demonstrou eficiência quimiopreventiva apenas para a menor dose (G5) e as porcentagens de redução de danos foram de 43,25 por cento em G5 e 18,47 por cento em G6. No momento T48 as porcentagens de redução de danos foram de 44,67 por cento e 37,76 por cento para G5 e G6, respectivamente.

Avaliação da mutagenicidade e antimutagenicidade de um biopolímero extraído do microorganismo Agrobacterium radiobacter em camundongos Swiss / Assessment of mutagenicity and antimutagenicity of a biopolymer extracted from the microorganism Agrobacterium radiobacter in mice

A presente pesquisa avaliou a ação mutagênica e antimutagênica de um biopolímero de glucose extraído da Agrobacterium radiobacter (Biopolímero de Agrobacterium radiobacter). O experimento foi realizado com camundongos Swiss machos divididos em oito grupos. O tratamento com o biopolímero foi realizado por gavage em dose única concomitante a uma dose de solução tampão fosfato nos grupos de avaliação da mutagenicidade, ou ao agente indutor de danos no DNA, ciclofosfamida, na concentração de 50 mg/kg (peso corpóreo - p.c.), nos grupos de avaliação da antimutagenicidade. Utilizou-se o teste de micronúcleo em sangue periférico e a coleta de sangue foi realizada 24 e 48 h após a aplicação das substâncias-teste. A análise estatística demonstrou que o biopolímero não possui atividade mutagênica e que é efetivo em prevenir danos no DNA. As porcentagens de redução de danos nos grupos de antimutagenicidade foram de 83,9 por cento, 89,1 por cento e 103,1 por cento em 24 h e 101,24 por cento, 98,14 por cento e 120,64 por cento em 48 h para as doses de 75, 150 e 300mg/kg (p.c.), respectivamente. A alta porcentagem de redução de danos associada à ausência de efeitos mutagênicos indica, além da atividade quimioprotetora, a possibilidade do biopolímero ser um alimento funcional candidato à utilização como co-adjuvante na quimioterapia para prevenir efeitos colaterais.

This study evaluated the mutagenic and ant mutagenic action of a biopolymer of glucose extracted from Agrobacterium radiobacter (Biopolymer of Agrobacterium radiobacter). The experiment was conducted with Swiss male mice divided into eight groups. Treatment with the biopolymer was performed in a single dose by gavage at a dose of concomitant phosphate buffer groups in the evaluation of mutagenicity, or the agent of inducing DNA damage, cyclophosphamide, the concentration of 50 mg/kg (body weight --b.w.), in groups of assessment ant mutagenic. We used the micronucleus test in peripheral blood. The blood sample was held 24 and 48 h after application of the test substances. Statistical analysis showed that the biopolymer has no mutagenic activity and it is effective in preventing damage to DNA. The percentages of damage reduction in groups of ant mutagenic were 83.9 percent, 89.1 percent and 103.1 percent in 24 h and 101.24 percent, 98.14 percent and 120.64 percent at doses of 48 to 75, 150 and 300 mg/kg (b.w.) respectively. The high percentage of damage reduction associated with the absence of mutagenic effects indicates the possibility of biopolymer chemoprotection action. It can also be considered a functional food candidate to be used as co-adjuvant chemotherapy to prevent side effects.