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Sharma, V and Shaheen, SS and Dixit, D and Sen, E (2012) Farnesyltransferase inhibitor manumycin targets IL1β-Ras-HIF-1α axis in tumor cells of diverse origin. Inflammation, 35 (2). pp. 516-519.

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Abstract

We have recently reported that Ras acts as an intermediate coactivator in IL-1β-mediated hypoxia-inducible factor-1α (HIF-1α) activation in glioblastoma multiforme (GBM). Since HIF-1α plays a crucial role in linking inflammatory and oncogenic pathways, we investigated whether this IL1β-Ras-HIF-1α signaling axis observed in GBM also exists in other tumors of diverse origin under normoxia. Treatment with IL-1β induced Ras in non-GBM cell lines A549 (lung), HeLa (cervical), and HepG2 (liver), and inhibition of Ras activity attenuated HIF-1α activity. Our findings suggest that Ras links IL-1β and HIF-1α in tumors of diverse origin. As we have previously reported that the farnesyltransferase inhibitor manumycin decreases Ras activity in glioma cells, we investigated whether manumycin could regulate IL-1β-mediated HIF-1α activation. Manumycin abrogated IL-1β-induced HIF-1α activation in both glioma and non-glioma tumor cells. In addition, manumycin also decreased IL-1β induced pro-inflammatory responses in tumor cells.

Item Type: Article
Subjects: Neurodegenerative Disorders
Neuro-Oncological Disorders
Neurocognitive Processes
Neuronal Development and Regeneration
Informatics and Imaging
Genetics and Molecular Biology
Depositing User: Dr. D.D. Lal
Date Deposited: 04 May 2017 04:25
Last Modified: 09 Jan 2018 04:02
URI: http://nbrc.sciencecentral.in/id/eprint/22

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