
DOI . ORG {
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Title[redir]:
Critical role of the death receptor pathway in the antitumoral effects induced by hispanolone derivatives | Oncogene
Description:
Labdane diterpenoids have a broad spectrum of biological activities including antibacterial, antiviral and anti-inflammatory properties. However, little is known about their possible role in the apoptotic cell death machinery. Here, we report that hispanolone derivatives, a group of labdane diterpenoids, induce apoptosis in different tumor cell lines by activating caspase-8 with subsequent participation of mitochondrial signaling. Activation of caspase-8 by hispanolone derivatives was followed by a decrease in mitochondrial membrane potential, the release of apoptotic factors from mitochondria to the cytosol, and activation of caspases-9 and 3. Hispanolone derivatives also led to a time-dependent cleavage of Bid. Inhibition of caspase-8 abrogated these processes, suggesting that the death receptor pathway has a critical role in the apoptotic events induced by hispanolone derivatives. In addition, silencing death receptors with small interfering RNA s or pretreating cells with neutralizing antibodies to Fas ligand, tumor necrosis factor receptor 1 (TNF-R1), and TNF-α receptor 2 (TRAIL) inhibited diterpenoid-induced apoptosis, revealing it to be dependent on these death receptors. Interestingly, hispanolone derivatives had no effect on non-tumor cells. Consistently, in vivo bioluminescence imaging corroborates this antineoplasic effect, as hispanolone derivatives significantly decrease cancer growth in tumor xenograft assays. These data demostrate the antitumoral effects of hispanolone derivatives and provide relevant preclinical validation for the use of these compounds as potent therapeutic agents in cancer treatment.
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Keywords {🔍}
article, google, scholar, cas, nature, apoptosis, death, cancer, derivatives, hispanolone, access, cell, activation, cells, content, information, las, caspase, cookies, oncogene, receptor, pathway, effects, diterpenoids, inhibition, chem, madrid, privacy, data, critical, role, heras, hortelano, open, rodriguez, pharmacol, lee, nfkappa, spain, antitumoral, través, lópezfontal, cuadrado, apoptotic, receptors, agents, activity, med, biol, lin,
Topics {✒️}
nature portfolio permissions reprints privacy policy author information authors nature 1996 nature advertising social media enhanced anti-tumor therapy cancer therapy-induced apoptosis experimental anti-leukemic drug kindly provide luc-b16f10 cold-water soluble polysaccharide lps-stimulated macrophage raw264 nitric oxide-dependent apoptosis inhibited diterpenoid-induced apoptosis natural origin-biological activities transcription factor nf-kappab springerlink instant access dna-binding activity permissions labdane-type diterpenoids ent-kaurene derivatives personal data silencing death receptors de las heras anti-inflammatory activity human cancer cells trail-induced apoptosis targeting death receptors data protection data demostrate anti-inflammatory properties andrographolide-induced apoptosis privacy inhibits nf-kappa apoptotic events induced facultad de farmacia small interfering rna issue learn apoptotic cell death exhibits antitumor activity 1h-indole derivatives nuclear factor kappa macrophage eicosanoid biosynthesis explore content subscription content death receptor pathway andrographolide attenuates inflammation cancer therapy
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headline:Critical role of the death receptor pathway in the antitumoral effects induced by hispanolone derivatives
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datePublished:2012-02-06T00:00:00Z
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headline:Critical role of the death receptor pathway in the antitumoral effects induced by hispanolone derivatives
description:Labdane diterpenoids have a broad spectrum of biological activities including antibacterial, antiviral and anti-inflammatory properties. However, little is known about their possible role in the apoptotic cell death machinery. Here, we report that hispanolone derivatives, a group of labdane diterpenoids, induce apoptosis in different tumor cell lines by activating caspase-8 with subsequent participation of mitochondrial signaling. Activation of caspase-8 by hispanolone derivatives was followed by a decrease in mitochondrial membrane potential, the release of apoptotic factors from mitochondria to the cytosol, and activation of caspases-9 and 3. Hispanolone derivatives also led to a time-dependent cleavage of Bid. Inhibition of caspase-8 abrogated these processes, suggesting that the death receptor pathway has a critical role in the apoptotic events induced by hispanolone derivatives. In addition, silencing death receptors with small interfering RNA s or pretreating cells with neutralizing antibodies to Fas ligand, tumor necrosis factor receptor 1 (TNF-R1), and TNF-α receptor 2 (TRAIL) inhibited diterpenoid-induced apoptosis, revealing it to be dependent on these death receptors. Interestingly, hispanolone derivatives had no effect on non-tumor cells. Consistently, in vivo bioluminescence imaging corroborates this antineoplasic effect, as hispanolone derivatives significantly decrease cancer growth in tumor xenograft assays. These data demostrate the antitumoral effects of hispanolone derivatives and provide relevant preclinical validation for the use of these compounds as potent therapeutic agents in cancer treatment.
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