Nanocurcumin-Mediated Down-Regulation of Telomerase Via Stimulating TGFβ1 Signaling Pathway in Hepatocellular Carcinoma Cells

Authors
Molood Shariati 1
Samira Hajigholami 1
Ziba Veisi Malekshahi 2
Maliheh Entezari 3
Narges Bodaghabadi 1
Majid Sadeghizadeh 1
1 Department of Molecular Genetics, School of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-154, Tehran, Iran
2 Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Biology, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran
10.22034/ibj.22.3.171
Abstract
Background: Curcumin, extracted from turmeric, represents enormous potential to serve as an anticancer agent. Telomerase is viewed as a prominent molecular target of curcumin, and transforming growth factor-β1 (TGFβ1) has proven to be a major inhibitory signaling pathway for telomerase activity. In the current study, we aimed to explore suppressive effects of nanocurcumin on telomerase expression through TGFβ1 pathway in a hepatocellular carcinoma cell line (Huh7). Methods: MTT assay was used to determine the effect of nonocurcumin on viability of Huh7 cells. RT-PCR was used to analyze the gene expression patterns. Results: MTT assay revealed that nanocurcumin acts in a dose- and time-dependent manner to diminish the cell viability.

RT-PCR analysis indicated that nanocurcumin results in augmentation of TGFβ1 72 hours post treatment and leads to the reduction of telomerase expression 48 and 72 hours post exposure. Also, up-regulation of Smad3 and E2F1 and down-regulation of Smad7 confirmed the effect of nanocurcumin on intermediate components of TGFβ1 pathway. Furthermore, transfection of the proximal promoter of telomerase triggered a significant

reduction in luciferase activity. Conclusion: The data from the present study lead us to develop a deeper understanding of the mechanisms underlying nanocurcumin-mediated regulation of telomerase expression, thereby presenting a new perspective to the landscape of using nanocurcumin as a cancer-oriented therapeutic agent.
Keywords
Hepatocellular Carcinoma
Telomerase
Gene expression