Butyrate Increases Apoptosis Induced by Different Antineoplastic Drugs in Monocytic Leukemia Cells

Ramos, Mariana Gontijo; Rabelo, Flávia L.A; Brumatti, Gabriela; Bueno-da-Silva, A. E. B.; Amarante-Mendes, Gustavo P.; Alvarez-Leite, Jacqueline I.

doi:10.1159/000081942

Cited by 17 publications

(18 citation statements)

References 43 publications

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“…P-OH has a rational molecular basis to be added to established therapeutic methods and the advantage that lower doses of chemotherapy are required to obtain better results [40,41] .…”

Section: Discussionmentioning

confidence: 99%

In vitro Induction of Apoptosis in U937 Cells by Perillyl Alcohol with Sensitization by Pentoxifylline: Increased BCL-2 and BAX Protein Expression

et al. 2006

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Background: Chemotherapy is effective against a wide variety of tumor cells, although its use is limited by side effects. In vitro experiments and phase I and II trials have shown that phytochemicals such as perillyl alcohol (P-OH) have antitumor effects. Pentoxifylline (PTX), a synthetic methylxanthine used mainly to treat pathologies associated with hematological diseases, sensitizes tumor cells to chemotherapy. The aim of this study was to determine whether PTX amplifies the antitumor effects of P-OH in U937 human myelomonocytic leukemia cells. Methods: Apoptosis was measured by the loss of mitochondrial membrane potential determined by flow cytometry using dihexyloxacarbocyanine iodide (DiOC₆) and propidium iodide. Bcl-2 and Bax protein expression was also assessed by Western blot analysis. Results: P-OH and PTX induced loss of the mitochondrial membrane potential in U937 cells in vitro. Culturing the cells in the presence of both compounds caused a significant increase (p < 0.001) in apoptosis and expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins. However, despite their coexistence, Bax expression prevailed in our experiments. These data suggest that the effects of PTX might be attributable to changes in the mitochondrial membrane potential. Conclusion: PTX sensitizes tumor cells to the anti-neoplastic action of P-OH. These observations may have clinical relevance in the treatment of cancer patients.

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“…P-OH has a rational molecular basis to be added to established therapeutic methods and the advantage that lower doses of chemotherapy are required to obtain better results [40,41] .…”

Section: Discussionmentioning

confidence: 99%

In vitro Induction of Apoptosis in U937 Cells by Perillyl Alcohol with Sensitization by Pentoxifylline: Increased BCL-2 and BAX Protein Expression

et al. 2006

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“…The supernatants were collected and incubated at 37 ° C with the reaction buffer supplied, which contained dithiothreitol and substrates, Asp-Glu-Val-Asp (DEVD)-p-nitroaniline (pNA) for caspase-3, Ile-Glu-Thr-Asp (IETD)-pNA for caspase-8 and Leu-Glu-His-Asp (LEHD)-pNA for caspase-9. The optical density of the reaction mixture was quantified spectrophotometrically at a wavelength of 405 nm [21] .…”

Section: In Vitro Caspase Activity Assaymentioning

confidence: 99%

Sanguinarine, a Benzophenanthridine Alkaloid, Induces Apoptosis in MDA-MB-231 Human Breast Carcinoma Cells through a Reactive Oxygen Species-Mediated Mitochondrial Pathway

Choi

Kim²,

Lee³

et al. 2008

Chemotherapy

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Background: Sanguinarine is a benzophenanthridine alkaloid that is known to have antimicrobial, anti-inflammatory, antioxidant and anticancer properties. In this study, we examined the effects of this compound on reactive oxygen species (ROS) production and the association of these effects with apoptotic tumor cell death using a human breast carcinoma MDA-MB-231 cell line. Methods: Cytotoxicity was evaluated by trypan blue exclusion methods. Apoptosis was detected using DAPI staining, agarose gel electrophoresis and flow cytometer. The expression levels of proteins were determined by Western blot analyses and caspase activities were measured using colorimetric assays. The ROS production and mitochondrial membrane potential (MMP, ΔΨ_m) changes were measured fluorimetrically. Results: The results of this study demonstrate that sanguinarine mediates ROS production, and that this mediation is followed by a decrease in MMP, the release of cytochrome c, activation of caspase-9 and caspase-3, and downregulation of antiapoptosis factor XIAP and cIAP-1. Sanguinarine also promoted the activation of caspase-8 and truncation of Bid (tBid). Moreover, the quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the sanguinarine-induced apoptosis effects via inhibition of ROS production, MMP collapse, tBid expression and the subsequent activation of caspases. These observations clearly indicate that ROS are involved in the early molecular events in the sanguinarine-induced apoptotic pathway. Conclusion: Our data imply that sanguinarine-induced ROS are key mediators of MMP collapse, which leads to the release of cytochrome c followed by caspase activation, culminating in apoptosis.

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“…Briefly, cells were lysed in a lysis buffer for 30 min on an ice bath. The lysed cells were centrifuged at 14,000 rpm for 10 min, and 100 g protein was incubated with 50 l of reaction buffer and 5 l of colorimetric tetrapeptides, DEVD-pNA for caspase-3, IETD-pNA for caspase-8 and LEHD-pNA for caspase-9, respectively, at 37 ° C for 2 h. The optical density of the reaction mixture was quantitated spectrophotometrically at a wavelength of 405 nm [21] .…”

Section: Assay Of Caspase-3 Caspase-8 and Caspase-9 Activitymentioning

confidence: 99%

Induction of Apoptosis by <i>(Z)</i>-Stellettic Acid C, an Acetylenic Acid from the Sponge <i>Stelletta</i> sp., Is Associated with Inhibition of Telomerase Activity in Human Leukemic U937 Cells

Park

Kim²,

Kim³

et al. 2007

Chemotherapy

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Background: (Z)-Stellettic acid C, an acetylenic acid from the marine sponge Stelletta sp., has been shown to have cytotoxic activity in some cancer cells; however, its mechanisms on malignant cell growth are not known. In this study, the potential of (Z)-stellettic acid C to induce apoptosis in human leukemic U937 cells and its effects on telomerase activity were investigated. Methods: Cytotoxicity was evaluated by MTT assays. Apoptosis was detected using DAPI staining and annexin V fluorescein. The mRNAs of Bcl-2, inhibitor of apoptosis proteins (IAPs) family and Fas/FasL system were determined by RT-PCR. Caspases and telomerase activities were measured using colorimetric assay and telomeric repeat amplification protocol enzyme-linked immunosorbent assay (TRAP-ELISA), respectively. Results: Exposure of U937 cells to (Z)-stellettic acid C resulted in growth inhibition and induction of apoptosis in a dose-dependent manner, which was associated with the modulation of Bcl-2 family expression, activation of caspases and downregulation of IAPs family members. (Z)-Stellettic acid C treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase, a main determinant of the telomerase enzymatic activity, was progressively downregulated by (Z)-stellettic acid C treatment. Conclusions: These results suggest that (Z)-stellettic acid C could have a possible cancer therapeutic potential.

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Butyrate Increases Apoptosis Induced by Different Antineoplastic Drugs in Monocytic Leukemia Cells

Cited by 17 publications

References 43 publications

In vitro Induction of Apoptosis in U937 Cells by Perillyl Alcohol with Sensitization by Pentoxifylline: Increased BCL-2 and BAX Protein Expression

In vitro Induction of Apoptosis in U937 Cells by Perillyl Alcohol with Sensitization by Pentoxifylline: Increased BCL-2 and BAX Protein Expression

Sanguinarine, a Benzophenanthridine Alkaloid, Induces Apoptosis in MDA-MB-231 Human Breast Carcinoma Cells through a Reactive Oxygen Species-Mediated Mitochondrial Pathway

Induction of Apoptosis by <i>(Z)</i>-Stellettic Acid C, an Acetylenic Acid from the Sponge <i>Stelletta</i> sp., Is Associated with Inhibition of Telomerase Activity in Human Leukemic U937 Cells

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