Narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma cells

Abstract

Cell motility and resistance to apoptosis characterize glioblastoma multiforme growth and malignancy. Narciclasine, a plant growth modulator, could represent a powerful new weapon targeting the Achilles' heel of glioblastoma multiforme and may offer the potential to better combat these devastating malignancies. The in vitro effects of narciclasine on cell proliferation, morphology, actin cytoskeleton organization, and the Rho/Rho kinase/LIM kinase/cofilin pathway and its antitumor activity in vivo have been determined in models of human glioblastoma multiforme. Narciclasine impairs glioblastoma multiforme growth by markedly decreasing mitotic rates without inducing apoptosis. The compound also modulates the Rho/Rho kinase/LIM kinase/cofilin signaling pathway, greatly increasing GTPase RhoA activity as well as inducing actin stress fiber formation in a RhoA-dependent manner. Lastly, the treatment of human glioblastoma multiforme orthotopic xenograft-bearing mice with nontoxic doses of narciclasine significantly increased their survival.Narciclasine antitumor effects were of the same magnitude as those of temozolomide, the drug associated with the highest therapeutic benefits in treating glioblastoma multiforme patients. Our results show for the first time that narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma multiforme cells and significantly increases the survival of human glioblastoma multiforme preclinical models. This statement is made despite the recognition that to date, irrespective of treatment, no single glioblastoma multiforme patient has been cured.

Differential Proteomics Analysis of Oligodendrogliomas and Astrocytomas Using iTRAQ Quantification

“…Also, pharmacologic inhibition of Ras in GBM resulted in decreased Rac1 activity, which was consistent with the findings under increased RhoA activation [26,27]. Treating glioblastoma cell with plant growth regulator Narciclasine led to increase ROCK activity and stress fiber formation, and these led to an increase in the survival rate of orthotopic transplanted tumor mice [16,28]. In the present work, we found RhoA is highly expressed in oligodendrogliomas but not astrocytomas.…”

RASSF1A Suppresses the Invasion and Metastatic Potential of Human Non–Small Cell Lung Cancer Cells by Inhibiting YAP Activation through the GEF-H1/RhoB Pathway

“…S8B). By using Narciclasine, a Rho activator (25), in RASSF1A-depleted HEBC-3 cells, we revealed that Rho proteins sustained activation impaired cell migration and invasion. As we had showed that active RhoAV14 had no effects on cell migration upon RASSF1A depletion, the Narciclasine effect could then mainly due to RhoB reactivation ( Supplementary Fig.…”

Narciclasine, a potential allelochemical, affects subcellular trafficking of auxin transporter proteins and actin cytoskeleton dynamics in Arabidopsis roots

“…Narciclasine (NCS) is a bioactive secondary metabolite (Amaryllidaceae alkaloid) isolated from Narcissus tazetta bulbs and also widely exists in the genera Galanthus, Haemanthus, Leucojum, Pancratium, Sprekelia, Sternbergia and Vallota (Piozzi et al 1969). Previous studies showed that NCS possesses antimitotic (Ceriotti 1967), antiviral functions (Gabrielsen et al 1992) and antitumor activities (Lefranc et al 2009). In laboratory studies, we have found that NCS exhibits a wide range of inhibitory effects on seed germination and seedling growth in rice, cabbage, Arabidopsis and lettuce (Bi et al 1998;Na et al 2011a, b;Hu et al 2014) and on chloroplast development of excised radish cotyledons (Bi et al 1998).…”