
DOI . ORG {
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Title[redir]:
Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases
Description:
Cyperus rotundus L. belongs to the Cyperaceae family and is a well documented traditional medicinal herb. Its rhizome has been reported to possess wide spectrum pharmacological activities including anti-inflammatory and antioxidant activity. However, the cellular and molecular mechanisms of the anticancer activity have not been elucidated. In the present study, we investigated the pro-apoptotic effects of C. rotundu rhizomes in a human breast carcinoma MDA-MB-231 cell model. Treatment of MDA-MB-231 cells with an ethanol extract of C. rotundu rhizomes (EECR) and a methanol extract of C. rotundu rhizomes (MECR), but not a water extract of C. rotundu rhizomes, resulted in potent antiproliferative activity. The activity of the EECR was higher than that of the MECR and was associated with the induction of apoptosis. The induction of apoptosis by the EECR was associated with upregulation of death receptor 4 (DR4), DR5 and pro-apoptotic Bax, as well as downregulation of anti-apoptotic survivin and Bcl-2. EECR treatment also downregulated Bid expression and activated caspase-8 and -9, the respective initiator caspases of the extrinsic and intrinsic apoptotic pathways. The increase in mitochondrial membrane depolarization was correlated with activation of effector caspase-3 and cleavage of poly(ADP-ribose) polymerase, a vital substrate of activated caspase-3. Blockage of caspase activation by pretreatment with a pan-caspase inhibitor consistently inhibited apoptosis and abrogated growth inhibition in EECR-treated MDA-MB-231 cells. Although reactive oxygen species (ROS) increased following treatment with the EECR, inhibiting ROS with a ROS scavenger did not attenuate EECR-induced apoptosis. Furthermore, inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathways failed to reverse EECR-induced apoptosis and growth inhibition. These results suggest that the pro-apoptotic activity of the EECR may be regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways that is not associated with ROS generation or the PI3K/Akt and MAPK pathways.
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Keywords {🔍}
cells, eecr, apoptosis, cell, caspase, mdamb, treatment, rotundus, article, view, cancer, pubmedncbi, google, scholar, eecrinduced, cyperus, apoptotic, activation, death, fig, extract, ros, dna, effects, protein, proteins, control, rhizomes, pathways, results, caspases, pathway, min, extracts, usa, assay, breast, activity, rotundu, mitochondrial, signaling, analysis, induction, ethanol, proapoptotic, growth, mapk, flow, μgml, family,
Topics {✒️}
pan-caspase inhibitor z-vad-fmk peroxidase-labeled donkey anti-rabbit z-vad-fmk completely abrogated c-jun nh2-terminal kinase dual-emission potential-sensitive probe metabolic-dye-based mtt assay mendeley abstract cyperus rotundus ile-glu-thr-asp 1021-335x online issn sheep anti-mouse immunoglobulin eecr-treated mda-mb-231 cells enzyme-linked immunosorbent assay n-acetyl l-cysteine 5-diphenyl-2h-tetrazolium bromide fructose-mediated protein glycoxidation bh3 pro-apoptotic protein home submit manuscript mda-mb-231 cell growth mda-mb-231 cells occurred nf-κb signaling pathways mitogen-activated protein kinase z-vad-fmk dose-dependent gradual increase traditional oriental medicine attenuate eecr-induced apoptosis reverse eecr-induced apoptosis affect eecr-induced apoptosis regulating eecr-induced apoptosis anti-apoptotic survivin decreased mda-mb-231 cells treated representative pi3k/akt inhibitor clinical oncology experimental activate membrane-proximal caspases receptor-mediated apoptotic stimuli inhibit eecr-induced apoptosis death receptor-mediated pathway pi3k/akt pathway plays eecr decreased pro-caspase-8 concentration-dependent manner compared eecr-induced antiproliferative effects skin human malignancy trypan blue exclusion pro-apoptotic bid protein oncology molecular caspase-8-mediated proteolytic activation pro-apoptotic bax expression previous pharmacological investigations remove unbound dye septic mice due specific synthetic substrates
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