5 research outputs found
Seletividade do nicosulfuron em linhagens e hÃbridos de milho.
O milho é uma das principais culturas da agricultura brasileira, não somente no aspecto produtivo, como também no que diz respeito à sua importância estratégica, por ser um dos principais componentes em rações para nutrição animal, servindo assim, consequentemente, como uma das bases para a alimentação humana. Um dos fatores que mais interferem na produtividade do milho em condições de campo é a competição com outras plantas que emergem no mesmo espaço, as chamadas plantas daninhas. Para o controle de plantas daninhas em plantios comerciais, a opção mais utilizada tem sido a aplicação de herbicidas, dentre os quais o nicosulfuron é um dos principais indicados para a cultura do milho. Entretanto, o emprego de herbicidas para o controle de plantas daninhas deve considerar a seletividade ao herbicida para a cultura. Plantas são consideradas como sensÃveis quando seu crescimento e desenvolvimento são alterados pela ação de um produto herbicida, enquanto a tolerância consiste na capacidade inata da planta sobreviver e se reproduzir após o tratamento herbicida, mesmo sofrendo injúrias (Vargas; Roman, 2006). Tanto a tolerância quanto a sensibilidade a herbicidas são caracterÃsticas altamente relacionadas com a variabilidade genética natural da espécie, e podem ser alteradas por pressão de seleção, mutação, cruzamento entre genótipos tolerantes e sensÃveis, e/ou biotecnologia.bitstream/item/178566/1/circ-237.pd
ASSESSMENT OF THE EFFECT OF SPHINGOSINE KINASE INHIBITORS ON APOPTOSIS, UNFOLDED PROTEIN RESPONSE AND AUTOPHAGY OF T-ACUTE LYMPHOBLASTIC LEUKEMIA CELLS: INDICATIONS FOR NOVEL THERAPEUTICS
Introduction. Sphingosine 1-phosphate (S1P) is involved in many
processes such as cell survival, growth, migration, and cancer. S1P is
formed by the phosphorylation of sphingosine by sphingosine kinase
1 (SK1) or sphingosine kinase 2 (SK2). While the role of SK1 in cancer
is well established, the role of SK2 in regulating apoptosis is still a matter
of debate, even though emerging evidence has highlighted the
importance of SK2 in cancer. Therefore, SKs represent a promising target
for cancer therapy. Recently, the importance of S1P in hematological
malignancies has been described. Here, we analyze the therapeutic
effects of 2-(p-Hydroxyanilino)-4-(p-chlorophenyl)thiazole (SKi), an
SK1/2 inhibitor, and (R)-FTY720 methyl ether (ROMe), a SK2-selective
inhibitor, in T-ALL cell lines. Methods. T- ALL cell lines (Molt-4, Jurkat,
CEM-R) were treated with SKi and ROMe for 40 h, then MTT assays
were performed to analyze cell viability. Apoptosis induction was evaluated
by Annexin V/PI staining. Protein expression was studied by
western blot (WB). Results. SKi and ROMe induced a decrease in cell viability,
as demonstrated by MTT assays. Annexin-V/PI staining and flow
cytometric analysis of cells treated with a SKi concentration equivalent
to the IC50 documented the occurrence of apoptotic cell death. This
was confirmed by WB analysis for caspase and PARP cleavage in all the
cell lines. However, we also observed a SKi-induced autophagy by
means of WB and transmission electron microscopy analysis in Jurkat
and CEM-R cells. We then analyzed the expression of ER stress/UPR
hallmarks. SKi activated the ER stress/UPR pathway and this occurred
following apoptosis and correlated with autophagy. The combination
of SKi and chloroquine (an autophagy inhibitor) induced a decrease in
cell viability, indicating that the UPR/autophagic response is likely to be
a protective mechanism. In Molt-4 cells, we detected an increase in SK1
expression after 40 h of treatment with SKi, that could represent an
attempt of cells to escape SKi-induced apoptosis, as high SK1 expression
is known to enhance cell growth and survival. Notably, SKi synergized
with vincristine at concentrations of SKi that were much below
its respective IC50, suggesting that vincristine sensitized T-ALL cells to
SKi and that combining chemotherapeutic agents with SK inhibitors
could be feasible in the treatment of T-ALL. Finally, ROMe treatment
induced an autophagic type of cell death. Conclusions. We report herein
that SKi and ROMe affect T-ALL cell viability, but they exert their
effects through different mechanisms. While ROMe induces an
autophagic cell death, SKi induces apoptosis. Moreover, for the first
time, we demonstrated that SKi activates an ER stress/UPR pathway in
T-ALL cells and this is linked with a protective autophagic response.
Thus, our findings indicate that SK1 or SK2 may represent potential
targets for treating T-ALL, thereby enabling better management of this
cancer
ASSESSMENT OF THE EFFECT OF SPHINGOSINE KINASE INHIBITORS ON APOPTOSIS, UNFOLDED PROTEIN RESPONSE AND AUTOPHAGY OF T-ACUTE LYMPHOBLASTIC LEUKEMIA CELLS: INDICATIONS FOR NOVEL THERAPEUTICS
Introduction. Sphingosine 1-phosphate (S1P) is involved in many
processes such as cell survival, growth, migration, and cancer. S1P is
formed by the phosphorylation of sphingosine by sphingosine kinase
1 (SK1) or sphingosine kinase 2 (SK2). While the role of SK1 in cancer
is well established, the role of SK2 in regulating apoptosis is still a matter
of debate, even though emerging evidence has highlighted the
importance of SK2 in cancer. Therefore, SKs represent a promising target
for cancer therapy. Recently, the importance of S1P in hematological
malignancies has been described. Here, we analyze the therapeutic
effects of 2-(p-Hydroxyanilino)-4-(p-chlorophenyl)thiazole (SKi), an
SK1/2 inhibitor, and (R)-FTY720 methyl ether (ROMe), a SK2-selective
inhibitor, in T-ALL cell lines. Methods. T- ALL cell lines (Molt-4, Jurkat,
CEM-R) were treated with SKi and ROMe for 40 h, then MTT assays
were performed to analyze cell viability. Apoptosis induction was evaluated
by Annexin V/PI staining. Protein expression was studied by
western blot (WB). Results. SKi and ROMe induced a decrease in cell viability,
as demonstrated by MTT assays. Annexin-V/PI staining and flow
cytometric analysis of cells treated with a SKi concentration equivalent
to the IC50 documented the occurrence of apoptotic cell death. This
was confirmed by WB analysis for caspase and PARP cleavage in all the
cell lines. However, we also observed a SKi-induced autophagy by
means of WB and transmission electron microscopy analysis in Jurkat
and CEM-R cells. We then analyzed the expression of ER stress/UPR
hallmarks. SKi activated the ER stress/UPR pathway and this occurred
following apoptosis and correlated with autophagy. The combination
of SKi and chloroquine (an autophagy inhibitor) induced a decrease in
cell viability, indicating that the UPR/autophagic response is likely to be
a protective mechanism. In Molt-4 cells, we detected an increase in SK1
expression after 40 h of treatment with SKi, that could represent an
attempt of cells to escape SKi-induced apoptosis, as high SK1 expression
is known to enhance cell growth and survival. Notably, SKi synergized
with vincristine at concentrations of SKi that were much below
its respective IC50, suggesting that vincristine sensitized T-ALL cells to
SKi and that combining chemotherapeutic agents with SK inhibitors
could be feasible in the treatment of T-ALL. Finally, ROMe treatment
induced an autophagic type of cell death. Conclusions. We report herein
that SKi and ROMe affect T-ALL cell viability, but they exert their
effects through different mechanisms. While ROMe induces an
autophagic cell death, SKi induces apoptosis. Moreover, for the first
time, we demonstrated that SKi activates an ER stress/UPR pathway in
T-ALL cells and this is linked with a protective autophagic response.
Thus, our findings indicate that SK1 or SK2 may represent potential
targets for treating T-ALL, thereby enabling better management of this
cancer