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Abstract
We describe the effect of a chemically characterized lipophilic extract obtained from Marthasterias glacialis L. against human breast cancer (MCF-7) and human neuroblastoma (SH-SY5Y) cell lines. Evaluation of DNA synthesis revealed that both cell lines were markedly affected in a concentration-dependent way, the SH-SY5Y cell line being more susceptible. Cell cycle arrest was observed, an effect induced by the sterol, ergosta-7,22-dien-3-ol, present in the extract. Morphological evaluation of treated cells showed the advent of lipid droplets and chromatin condensation compatible with apoptosis, which was confirmed by the evaluation of caspase-3 and -9 activities. Palmitic acid was the main compound responsible for this apoptotic effect by a ceramide-independent mechanism that involved endoplasmic reticulum (ER)-stress with upregulation of CCAAT/-enhancer-binding protein homologous protein (CHOP).
Highlights
Nature is an indisputable source of drugs for the human pharmacotherapeutical arsenal [1,2,3]
We evaluated the activity of a purified lipophilic extract from M. glacialis on the cancer cell lines, MCF-7 and SH-SY5Y, and investigated the mechanism involved in cell death and cell cycle arrest
In this work, we studied the intrinsic pathway of apoptosis, nowadays it is known that, in some situations, CCAAT/-enhancer-binding protein homologous protein (CHOP) can result in the activation of the extrinsic pathway as a consequence of DR5 upregulation caused by the modulation of CHOP on the promoter of this superfamily
Summary
Nature is an indisputable source of drugs for the human pharmacotherapeutical arsenal [1,2,3]. The effect of a purified extract upon several human cancer and non-cancer cells was reported [8,11], though the mechanism responsible for the anticancer activity has not been investigated. In the particular case of PERK, its active form phosphorylates eIF2, which inhibits protein translation In this branch of UPR, the DNA-damage-inducible gene 153 (GADD153), known as C/EBP homologous protein (CHOP, a member of the C/EBP transcription factor family that heterodimerizes with other C/EBPs), is upregulated, and for this reason, it is a widely used marker of ER-stress [12,13,14]. We evaluated the activity of a purified lipophilic extract from M. glacialis on the cancer cell lines, MCF-7 (estrogen receptor positive human breast cancer cells) and SH-SY5Y (human neuroblastoma cells), and investigated the mechanism involved in cell death and cell cycle arrest. The contribution of the main compounds present in the extract (20 μM palmitic acid, 30 μM cis 11-eicosenoic acid, 10 μM cis 11,14-eicosadienoic acid and 25 μM ergosta-7,22-dien-3-ol) is discussed
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