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Ficus carica Latex Prevents Invasion Through Induction of Let-7d Expression in GBM Cell Lines

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Abstract

Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs and dietary plants has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Ficus carica (fig) latex (FCL) has been determined in a few cancer types, the effect of this latex on GBM tumors has not been investigated. Therefore, in the current study, the anti-proliferative activity of FCL and the effect of the FCL–temozolomide (TMZ) combination were tested in the T98G, U-138 MG, and U-87 MG GBM cell lines using the WST-1 assay. The mechanism of cell death was analyzed using Annexin-V/FITC and TUNEL assays, and the effect of FCL on invasion was tested using the chick chorioallantoic membrane assay. To determine the effect of FCL on GBM progression, the expression levels of 40 GBM associated miRNAs were analyzed in T98G cells using RT-qPCR. According to the obtained data, FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergistically increased in combination with TMZ. In addition, the current study is the first to demonstrate the effect of FCL on modulation of let-7d expression, which may be an important underlying mechanism of the anti-invasive effect of this extract.

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Acknowledgments

This work was supported by the Science Foundation of Uludag University (Project number; UAP(T)-2012/2 and HDP(T)-2013/3). This study was performed as part of G. Tezcan’s PhD thesis project.

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Authors and Affiliations

  1. Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey

    Gulcin Tezcan, Berrin Tunca, Gulsah Cecener & Unal Egeli

  2. Department of Neurosurgery, Medical Faculty, Uludag University, Bursa, Turkey

    Ahmet Bekar & Mevlut Ozgur Taskapilioglu

  3. Department of Physiology, Veterinary Medicine Faculty, Uludag University, Bursa, Turkey

    Murat Yalcin, Gokcen Guvenc, Gozde Yilmaz & Leman Gizem Erkan

  4. Department of Chemistry, Science Faculty, Uludag University, Bursa, Turkey

    Saliha Sahin & Cevdet Demir

  5. Department of Microbiology, Medical Faculty, Uludag University, Bursa, Turkey

    Ferah Budak

  6. Department of Biology, Science Faculty, Uludag University, Bursa, Turkey

    Hulusi Malyer

  7. Department of Medical Oncology, Medical Faculty, Uludag University, Bursa, Turkey

    Turkkan Evrensel

  8. Department of Histology and Embryology, Medical Faculty, Zirve University, Gaziantep, Turkey

    Ayhan Bilir

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  1. Gulcin Tezcan
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Correspondence to Berrin Tunca.

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Tezcan, G., Tunca, B., Bekar, A. et al. Ficus carica Latex Prevents Invasion Through Induction of Let-7d Expression in GBM Cell Lines. Cell Mol Neurobiol 35, 175–187 (2015). https://doi.org/10.1007/s10571-014-0109-y

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