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RETRACTED ARTICLE

Coronarin D, a labdane diterpene, inhibits both constitutive and inducible nuclear factor-kappa B pathway activation, leading to potentiation of apoptosis, inhibition of invasion, and suppression of osteoclastogenesis.
Mol Cancer Ther. 2008 Oct; 7(10):3306-17.MC

Abstract

Compounds isolated from members of the Zingiberaceae family are traditionally used as a medicine against inflammatory diseases, but little is known about the mechanism. Here, we report the isolation and structural identification of coronarin D [E-labda-8(17),12-diene-15-ol], a labdane-type diterpene, from Hedychium coronarium and delineate its mechanism of action. Because the transcription factor nuclear factor-kappaB (NF-kappaB) is a key mediator of inflammation, apoptosis, invasion, and osteoclastogenesis, we investigated the effect of coronarin D on NF-kappaB activation pathway, NF-kappaB-regulated gene products, and NF-kappaB-regulated cellular responses. The coronarin D inhibited NF-kappaB activation induced by different inflammatory stimuli and carcinogens. This labdane also suppressed constitutive NF-kappaB activity in different cell lines and inhibited IkappaBalpha kinase activation, thus leading to the suppression of IkappaBalpha phosphorylation, degradation, p65 nuclear translocation, and reporter gene transcription. Coronarin D also inhibited the NF-kappaB-regulated gene products involved in cell survival (inhibitor of apoptosis protein 1, Bcl-2, survivin, and tumor necrosis factor receptor-associated factor-2), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), invasion (matrix metalloproteinase-9), and angiogenesis (vascular endothelial growth factor). Suppression of these gene products by the diterpene enhanced apoptosis induced by TNF and chemotherapeutic agents, suppressed TNF-induced cellular invasion, and abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis. Coronarin D was found to be more potent than its analogue coronarin D acid. Overall, our results show that coronarin D inhibited NF-kappaB activation pathway, which leads to inhibition of inflammation, invasion, and osteoclastogenesis, as well as potentiation of apoptosis.

Authors+Show Affiliations

Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Unit 143, 1515 Holcombe Boulevard, Houston, TX 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Retracted Publication

Language

eng

PubMed ID

18852134

Citation

Kunnumakkara, Ajaikumar B., et al. "Coronarin D, a Labdane Diterpene, Inhibits Both Constitutive and Inducible Nuclear Factor-kappa B Pathway Activation, Leading to Potentiation of Apoptosis, Inhibition of Invasion, and Suppression of Osteoclastogenesis." Molecular Cancer Therapeutics, vol. 7, no. 10, 2008, pp. 3306-17.
Kunnumakkara AB, Ichikawa H, Anand P, et al. Coronarin D, a labdane diterpene, inhibits both constitutive and inducible nuclear factor-kappa B pathway activation, leading to potentiation of apoptosis, inhibition of invasion, and suppression of osteoclastogenesis. Mol Cancer Ther. 2008;7(10):3306-17.
Kunnumakkara, A. B., Ichikawa, H., Anand, P., Mohankumar, C. J., Hema, P. S., Nair, M. S., & Aggarwal, B. B. (2008). Coronarin D, a labdane diterpene, inhibits both constitutive and inducible nuclear factor-kappa B pathway activation, leading to potentiation of apoptosis, inhibition of invasion, and suppression of osteoclastogenesis. Molecular Cancer Therapeutics, 7(10), 3306-17. https://doi.org/10.1158/1535-7163.MCT-08-0432
Kunnumakkara AB, et al. Coronarin D, a Labdane Diterpene, Inhibits Both Constitutive and Inducible Nuclear Factor-kappa B Pathway Activation, Leading to Potentiation of Apoptosis, Inhibition of Invasion, and Suppression of Osteoclastogenesis. Mol Cancer Ther. 2008;7(10):3306-17. PubMed PMID: 18852134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coronarin D, a labdane diterpene, inhibits both constitutive and inducible nuclear factor-kappa B pathway activation, leading to potentiation of apoptosis, inhibition of invasion, and suppression of osteoclastogenesis. AU - Kunnumakkara,Ajaikumar B, AU - Ichikawa,Haruyo, AU - Anand,Preetha, AU - Mohankumar,Chiramel J, AU - Hema,Padmanabhan S, AU - Nair,Mangalam S, AU - Aggarwal,Bharat B, PY - 2008/10/15/pubmed PY - 2008/11/13/medline PY - 2008/10/15/entrez SP - 3306 EP - 17 JF - Molecular cancer therapeutics JO - Mol Cancer Ther VL - 7 IS - 10 N2 - Compounds isolated from members of the Zingiberaceae family are traditionally used as a medicine against inflammatory diseases, but little is known about the mechanism. Here, we report the isolation and structural identification of coronarin D [E-labda-8(17),12-diene-15-ol], a labdane-type diterpene, from Hedychium coronarium and delineate its mechanism of action. Because the transcription factor nuclear factor-kappaB (NF-kappaB) is a key mediator of inflammation, apoptosis, invasion, and osteoclastogenesis, we investigated the effect of coronarin D on NF-kappaB activation pathway, NF-kappaB-regulated gene products, and NF-kappaB-regulated cellular responses. The coronarin D inhibited NF-kappaB activation induced by different inflammatory stimuli and carcinogens. This labdane also suppressed constitutive NF-kappaB activity in different cell lines and inhibited IkappaBalpha kinase activation, thus leading to the suppression of IkappaBalpha phosphorylation, degradation, p65 nuclear translocation, and reporter gene transcription. Coronarin D also inhibited the NF-kappaB-regulated gene products involved in cell survival (inhibitor of apoptosis protein 1, Bcl-2, survivin, and tumor necrosis factor receptor-associated factor-2), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), invasion (matrix metalloproteinase-9), and angiogenesis (vascular endothelial growth factor). Suppression of these gene products by the diterpene enhanced apoptosis induced by TNF and chemotherapeutic agents, suppressed TNF-induced cellular invasion, and abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis. Coronarin D was found to be more potent than its analogue coronarin D acid. Overall, our results show that coronarin D inhibited NF-kappaB activation pathway, which leads to inhibition of inflammation, invasion, and osteoclastogenesis, as well as potentiation of apoptosis. SN - 1535-7163 UR - https://www.unboundmedicine.com/medline/citation/18852134/Coronarin_D_a_labdane_diterpene_inhibits_both_constitutive_and_inducible_nuclear_factor_kappa_B_pathway_activation_leading_to_potentiation_of_apoptosis_inhibition_of_invasion_and_suppression_of_osteoclastogenesis_ L2 - http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18852134 DB - PRIME DP - Unbound Medicine ER -