Euphol from Tapinanthus sp. Induces Apoptosis and Affects Signaling Proteins in Glioblastoma and Prostate Cancer Cells

BACKGROUND: Plants play an important role in cancer therapy. They are source of natural molecules which can induce apoptosis in cancer cells by affecting molecular mechanisms implicated in cancer progression. The MAP Kinase/ERK1/2 and PI3K/AKT signaling pathways are two classical signaling pathways implicated in cancer progression and constitute therapeutic targets against cancer. This study aimed to evaluate the effect of euphol on MAP Kinase/ERK1/2 and PI3K/AKT signaling pathways in glioblastoma and prostate cancer cells. Euphol is a tetracyclique triterpene alcohol isolated from Tapinanthus sp. which is a hemi parasitic plant belonging to Loranthaceae family. METHODS: Plant powder was extracted by maceration and euphol was isolated and described using respectively column chromatography separation on silica gel and spectroscopic data. Cytotoxic effect of euphol was evaluated using XTT assay and its effect on MAP Kinase/ERK1/2 and PI3K/AKT protein expression was investigated by Western immunoblot analysis. Apotosis was analyzed by evaluating caspase-3/7 activity. RESULTS: Our investigations demonstrated that this compound has an important cytotoxic effect on C6 and U87 MG glioblastoma (GBM) cells and PC-3 prostate cancer cells. Furthermore, euphol-induced apoptosis revealed by elevated caspase 3/7 activity, was correlated with a significant inhibition of MAP kinase/Erk 1/2 and PI3K/Akt signaling pathway in glioblastoma U87 MG cells. The reverse effect was observed in C6 glioblastoma cells, where apoptosis was correlated with a long-lasting activation of Erk 1/2.  In PC-3 cells, euphol had no or limited effect on Erk 1/2 and Akt activity. CONCLUSION: These results indicate that euphol induces cell death in glioblastoma and prostate cancer cells and regulates significantly Erk1/2 and Akt activity in glioblastoma cells.

A new abietane-type diterpenoid from roots of Burkea africana Hook (Fabaceae) with α-amylase inhibitory potential.

A new abietane-type diterpenoid, rubesanolidic acid (1), alongside six known compounds including ß-sitosterol (2), lupeol (3), betulinic acid (4) ursolic acid (5), ß-sitosterol 3-O-ß-D-glucopyranoside (6) and stigmasterol 3-O-ß-D-glucopyranoside (7) were isolated from the roots of Burkea africana through column chromatography. Their structures were elucidated from spectroscopic analyses (UV, IR, MS, 1D and 2D NMR) data and by comparison with data from previous studies. The extract and compounds were tested for their α-amylase inhibition. The extract was more active than the isolated compounds with a percentage inhibition of 51.0 ± 2.5% at 400 µg/mL and was the only sample showing above 50% inhibition at this dose. Amongst the isolated compounds and at the dose of 400 µg/mL, the new diterpenoid Rubesanolidic acid exibited the highest percentage inhibition of α-amylase of 38.2 ± 2.0% while ß-sitosterol showed the lowest inhibition of 9.6 ± 0.5%. The results indicate that B. africana is a potential source of antidiabetic compounds.

A new flavonoid glycoside from Tapinanthus sp. (Loranthaceae) and evaluation of anticancer activity of extract and some isolated compounds.

The present work describes the isolation and anticancer activity of Tapinanthus sp. which is a hemi parasitic plant harvested on Combretum glutinosum, the host plant. Phytochemical study afforded a new flavonoid glycoside, tapinantoside (1) isolated for the first time from natural source, alongside six known compounds (2-7). Structure of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, mass spectrometry and by comparison with literature data. The anticancer activity of extract and some isolated compounds were evaluated on glioblastoma (U87MG, C6) and prostate (PC-3) cancer cells. The methanol leaves extract showed good anticancer activity against U87 (IC50 = 21.40 µg/mL) and PC-3 cells (IC50 = 10.26 µg/mL). Compound 3 powerfully inhibits the proliferation of C6 (IC50 = 38.84 µM) and PC-3 cells (IC50 = 21.33 µM), while its effect was moderated on U87MG cells. Compound 1 and 7 were not active on all tested cancer cell lines.

Anticancer Activity of Combretum fragrans F. Hoffm on Glioblastoma and Prostate Cancer Cell Lines.

BACKGROUND: Cancer incidence has been growing in an alarming rate worldwide and new therapeutics are needed, particularly for intractable and chemoresistant cases. We evaluated the cytotoxic effects of Combretum fragrans F. Hoffm (Combretaceae) on glioblastoma (U87MG and C6) and prostate (PC-3) cancer cell lines. METHODS: The cytotoxic effect of the methanolic extract of the stem bark of Combretum fragrans was assessed using XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Expressions of Akt and ERK1/2 were determined using Western blot technique, while Caspase-3/7 kits were used to evaluate caspase-3/7 activity. RESULTS: C. fragrans extract inhibited the proliferation of U87 (IC50 = 20.13 µg/mL), C6 (IC50 = 12.17 µg/mL), and PC-3 (IC50 = 11.50 µg/mL) cells. Treatment with the extract resulted in lower levels (p < 0.001) of phospho-ERK1/2 and phospho-Akt in U87 cells, and instead, higher levels of phospho-ERK1/2 (p < 0.001) in C6 and PC-3 cells. An increase in caspase-3/7 activity was observed, mainly after 24 hours of treatment, indicating the activation of apoptotic processes. CONCLUSION: Altogether, these results suggest that C. fragrans have potent anticancer properties. This plant should be further investigated for developing new anticancer drugs.