Catechol cytotoxicity in vitro: Induction of glioblastoma cell death by apoptosis

Abstract

<jats:p> The exposure to benzene is a public health problem. Although the most well-known effect of benzene is hematopoietic toxicity, there is little information about the benzene and its metabolites effects on the central nervous system (CNS). This study examined the toxic effects of 1,2-dihydroxybenzene (catechol), a benzene metabolite, to human glioblastoma GL-15 cells. GL-15 cell cultures were used as a model to provide more information about the toxic effects of aromatic compounds to the CNS. Catechol induced time- and concentration-dependent cytotoxic effects. Morphological changes, such as the retraction of the cytoplasm and chromatin clumping, were seen in cells exposed to 200 μM catechol for 48 hours. In cells exposed to 600 μM catechol for 48 hours, 78.0% of them presented condensed nuclei, and the Comet assay showed DNA damage. The percentage of cells labeled with annexin V (apoptotic cells) was greater in the group exposed to catechol (20.7%) than in control cells (0.4%). Exposure to catechol at concentrations greater than 100 μM enhanced Bax levels, and a decrease in Bcl-2 level was observed after the exposure to 600 μM catechol for 48 hours. Furthermore, catechol depleted reduced glutathione. Hence, catechol induced cell death mainly by apoptosis. </jats:p>

Phenolic metabolites of benzene induced caspase-dependent cytotoxicities to K562 cells accompanied with decrease in cell surface sialic acids

“…Indeed, phenol at 1 mM did not cause an increase in phosphatidylserine exposure in K562 cells. Catechol has been demonstrated to induce apoptosis in glial cells, glioblastoma cells, neuroblastoma cells, glandular stomach cells, HL60 cells, and CD34+ progenitor cells (Moran et al, ; Hirose et al, ; Bironaite et al, ; Lima et al, ; de Oliveira et al, ; Mansoor et al, ). After exposure to hydroquinone, cell apoptosis occurred in various cells (Kerzic et al,; Shen et al,; Ibuki and Goto, ; Inayat‐Hussain et al, ; Rubio et al,; Yang et al, ; Lee et al, ).…”

“…These results indicated that inhibition of erythroid differentiation played a role in benzene exposure‐induced erythropoietic depression. On the other hand, it has been reported that benzene metabolites, including phenol, catechol, hydroquinone, and 1,2,4‐benzenetriol, induced apoptosis in various types of cells (Moran et al, ; Bironaite et al, ; Inayat‐Hussain et al, ; Yamamoto et al, ; de Oliveira et al, ; Rubio et al, ; Yang et al, ; Lee et al, ) . It was suggested that benzene metabolites‐induced apoptosis should be involved in benzene‐induced erythropoietic depression.…”

Antiplatelet Effect of Catechol Is Related to Inhibition of Cyclooxygenase, Reactive Oxygen Species, ERK/p38 Signaling and Thromboxane A2 Production

“…Catechol is not toxic to glioblastoma cells at concentrations below 0.2 mM [30]; however, it induces a 44% increase in esophageal cell death at 35 µM [4], suggesting that it exhibits differential cytotoxicity that is cell type-dependent.…”

8-Methoxypsoralen is a competitive inhibitor of glutathione S-transferase P1-1

“…The cells were permeabilized in methanol at −20°C for 10 min and incubated with the primary antibody (rabbit polyclonal IgG anti GSTP1/2—Santa Cruz®, 1:500) for 1 h. Subsequently, cells were rinsed three times with PBS, incubated with the secondary antibody (Conjugated Alexa Fluor® 546 goat anti-rabbit IgG—Invitrogen®, 1:400) and finally observed by fluorescence microscopy (Olympus AX70 microscope—green filter). Nuclei were stained by the dye Hoechst 33258 (ex/em 340/510 nm) (Oliveira et al, 2010). For negative control, cells were incubated with only secondary antibody under the same conditions described above.…”