Some biochemical consequences of feeding excesses of phenylalanine to rats.
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Biomedical subjects
M F Ryan
Publications and source records attributed to M F Ryan.
Effects of the polyacetylene capillin on human tumour cell lines.
We investigated the effects of capillin, a constituent of Artemisia monosperma, on four human tumour cell lines: colon carcinoma H729, pancreatic carcinoma MIA PaCa-2, epidermoid carcinoma of the larynx HEp-2 and lung carcinoma A549. Cells were treated with capillin to examine both the anti-proliferative and pro-apoptotic effects, as well as the molecular mechanism underlying these effects. Changes in cell proliferation, membrane permeability, macromolecular synthesis, glutathione (GSH), cell cycle and programmed cell death were evaluated. Capillin (1microM-10microM) inhibited cell proliferation and decreased macromolecular synthesis simultaneously, in a dose- and time-dependent manner. Co-incubation with L-buthionine sulfoximine (L-BSO) augmented the efficacy of capillin. Capillin modulated GSH levels, accumulated cells in the S+G2/M-phase of the cell cycle and induced cell death and DNA fragmentation, as indicated by flow cytometry, fluorescence microscopy and DNA fragmentation assay. These findings suggest that capillin has cytotoxic activity and can induce apoptosis in human tumour cell lines.
Alkynes↗
Effects of alpha-hederin and thymoquinone, constituents of Nigella sativa, on human cancer cell lines.
The separate effects of alpha-hederin and thymoquinone, the two principal bioactive constituents of Nigella sativa, on four human cancer cell lines [A549 (lung carcinoma), HEp-2 (larynx epidermoid carcinoma), HT-29 (colon adenocarcinoma) and MIA PaCa-2 (pancreas carcinoma)] were investigated. Alpha-hederin was also examined as a pro-drug. Each assessment quantified both cytotoxic and apoptotic/necrotic effects. Alpha-hederin and thymoquinone separately induced a dose- and time-dependent effect on the cell lines tested. HEp-2 cells were the most sensitive, exhibiting apoptosis with a higher incidence following thymoquinone treatment. Pre-treatment of cells with alpha-hederin, followed by thymoquinone or cisplatin, did not enhance the cytotoxicity or apoptosis induced by either drug. So, the membrane-perforating properties associated with saponins, here represented by alpha-hederin, enhance neither cytotoxicity nor apoptosis of these cancer cells.
Adenocarcinoma↗
Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells.
Our previous studies on active constituents of Nigella sativa have indicated that cell death induced by thymoquinone and alpha-hederin was dose- and time-dependent, in a range of four cancer cell lines. Both compounds elicited necrosis and apoptosis with a higher incidence of the latter induced by thymoquinone. As HEp-2 human laryngeal carcinoma cells were the most susceptible, we sought to better understand the mechanisms involved by using buthionine sulfoximine (BSO), a selective inhibitor of glutathione (GSH) synthesis, to determine the importance of GSH in the apoptosis elicited, using cisplatin as internal standard. BSO significantly enhanced alpha-hederin- and cisplatin- mediated toxicity as assessed by the MIT assay, without changes in apoptosis or necrosis levels. Although the MTI assay did not indicate BSO potentiation of thymoquinone, apoptosis levels were significantly enhanced following this combination, without changes in necrosis. Thymoquinone and cisplatin significantly decreased GSH levels in a dose-dependent manner, with BSO pre-treatment synergistically depleting GSH levels in only thymoquinone- treated cells. As the caspase 3 inhibitor, Z-DEVD-fmk significantly decreased thymoquinone- and cisplatin-induced apoptosis, GSH depletion and caspase 3-activation mediate thymoquinone-induced apoptosis, in this cell line.
Antineoplastic Combined Chemotherapy Protocols↗