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.

Nutritional and pharmacological importance of Ficus carica - A review

“…To determine the effect of Ficus carica latex on Glioblastoma multiforme progression, the expression levels of 40 Glioblastoma multiforme associated miRNAs were analyzed in T98G cells using RT-qPCR. Results showed that Ficus carica latex causes cell death in Glioblastoma multiforme cells with different responses to Ficus carica latextemozolomide combination, and this effect was synergistically increased in combination with temozolomide [102]. The aerial components of Ficus carica were examined to assess phototoxic activity on human melanoma cells.…”

microRNA cluster MC‐let‐7a‐1~let‐7d promotes autophagy and apoptosis of glioma cells by down‐regulating STAT3

“…Evidence was obtained by exploration of the miRBase website indicating that let‐7d, let‐7a‐1, and let‐7f‐1 belonged to the miR cluster MC‐let‐7a‐1 ~ let‐7d, which was selected for the subsequent experimentation. The let‐7 family is generally considered to be a cancer suppressor which has been evidenced by its distinct down‐regulation in a variety of tumors . Taken together, miR cluster MC‐let‐7a‐1 ~ let‐7d may have the potential to regulate glioma cell autophagy and apoptosis by targeting STAT3 in glioma.…”

“…As short noncoding endogenous RNAs, microRNAs (miRNAs) have been validated to engage in the glioma progression . For example, ectopic expression of let‐7d is involved in the suppressive role of Ficus carica Latex in GBM cell invasion . Furthermore, a study has indicated the suppressive influence of let‐7a over‐expression on glioma cell malignancy .…”

Ficus Carica and Its Constituents Role in Management of Diseases

“…A mixture of 6-O-acyl-beta-D-glucosyl-betasitosterols was isolated as an effective cytotoxic agent from fig latex and result confirmed in vitro inhibitory effects on proliferation of various cancer cell lines [32]. Antiproliferative activity of F. carica (fig) latex (FCL) and the effect of the FCL-temozolomide (TMZ) combination were examined in the cell lines such as T98G, U-138 MG, and U-87 MG glioblastoma multiforme (GBM) and data of the results showed latex FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergistically increased in combination with TMZ [33]. Anticancer effect of fig tree latex on human cancer cells was evaluated and results confirmed that there was a significant change in 10 mg/ml treatment of latex after 72 hrs on esophageal cancer line and 10 mg/ml was the optimum concentration in the inhibition of cell line growth [34].…”