title: Ficus carica latex prevents invasion through induction of let-7d expression in GBM cell lines.
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.
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Tezcan
authors.forename: Berrin
authors.initials: B
authors.lastname: Tunca
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bekar
authors.forename: Murat
authors.initials: M
authors.lastname: Yalcin
authors.forename: Saliha
authors.initials: S
authors.lastname: Sahin
authors.forename: Ferah
authors.initials: F
authors.lastname: Budak
authors.forename: Gulsah
authors.initials: G
authors.lastname: Cecener
authors.forename: Unal
authors.initials: U
authors.lastname: Egeli
authors.forename: Cevdet
authors.initials: C
authors.lastname: Demir
authors.forename: Gokcen
authors.initials: G
authors.lastname: Guvenc
authors.forename: Gozde
authors.initials: G
authors.lastname: Yilmaz
authors.forename: Leman Gizem
authors.initials: LG
authors.lastname: Erkan
authors.forename: Hulusi
authors.initials: H
authors.lastname: Malyer
authors.forename: Mevlut Ozgur
authors.initials: MO
authors.lastname: Taskapilioglu
authors.forename: Turkkan
authors.initials: T
authors.lastname: Evrensel
authors.forename: Ayhan
authors.initials: A
authors.lastname: Bilir
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005591:Chemical Fractionation; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D030681:Ficus / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007840:Latex / Q000494:pharmacology / Q000627:therapeutic use*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D018919:Neovascularization, Physiologic / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D007840:Latex; D035683:MicroRNAs; D010936:Plant Extracts; C487931:mirnlet7 microRNA, human; D003606:Dacarbazine; D000077204:Temozolomide