Abstract
BackgroundHyperactivation of mechanistic target of rapamycin (mTOR) signaling pathway is involved in the regulation of cellular growth, proliferation, and more in general, is a common phenomenon in most types of cancers. Thus, natural substances targeting this pathway can be of great therapeutic potential in supporting the treatment of tumor patients. Rhus tripartita (Ucria) Grande is a plant growing in desertic areas which is traditionally used for the treatment of several diseases in Tunisia. In the present work, the biochemical profile of the main compounds present in the plant leaf extract was determined and the anti-leukemic potential of the plant extracts against acute monocytic leukaemia (AML) THP-1 cells was investigated.MethodsAfter HPLC identification of some phenolic compounds present in the plant extract and the quantification of saponin content, the cytotoxic effect of Rhus tripartita extracts on THP-1 cell culture was evaluated using the colorimetric MTT assay for cell viability. THP-1 cells were incubated with medium containing the relative IC50 concentrations of total plant extract, saponin extract and some standard compounds (rutin (R); kaempferol (K); mixture of catechin, epicatechin, and epicatechin-gallate (CEEG); ellagic acid (EA). Finally, qRT-PCR and western blotting analysis were used to evaluate the effect of some flavonoids present in a crude extract of polyphenols and the total extract of saponins on cell survival and apoptosis.ResultsAnalysis of expression level of some gene (PIK3CA, PTEN, AKT1, mTOR, EIF4E, RPS6KB1, and TSC1) involved in the mTOR pathway and the phosphorylation of S6 and AKT proteins allowed to observe that a total Rhus tripartita extract and some of the compounds found in the extract controls THP-1 cell proliferation and apoptosis via regulation of the PI3K-Akt-mTOR signaling pathway.ConclusionRhus tripartita-induced inhibition of cell cycle and induction of apoptosis may involve the mTOR pathway. Therefore, Rhus tripartita extract may be a useful candidate as a natural anti-cancer drug to support the treatment of AML.
Highlights
Hyperactivation of mechanistic target of rapamycin signaling pathway is involved in the regulation of cellular growth, proliferation, and more in general, is a common phenomenon in most types of cancers
Aromatic plants used in folk medicine and in phytotherapy contain a high number of chemically diverse and structurally complex polyphenols holding a number of benefits such as an added economical value, lack of toxic effects, and inherent biological activities that make them attractive candidates for new therapies [2]
Epicatechin and epicatechin-gallate reached the total amount of almost 7 mg/100 g dry weight (DW) and were tested together, as a pool, for the remaining analyses
Summary
Hyperactivation of mechanistic target of rapamycin (mTOR) signaling pathway is involved in the regulation of cellular growth, proliferation, and more in general, is a common phenomenon in most types of cancers. Natural substances targeting this pathway can be of great therapeutic potential in supporting the treatment of tumor patients. A large number of scientific reports have demonstrated that medicinal plants from different geographical areas of the world are a rich source of biologically active compounds that can support treatments of various diseases, including some types of cancers. Belonging to the polyphenolic molecules group, flavonoids include almost 10,000 different compounds organized in subclasses as flavonols, flavan-3-ols, anthocyanins, flavanones, flavones, isoflavones and proanthocyanidins. These phytochemical classes show antibacterial, antiviral, anti-inflammatory, antilipidemic, or antidiabetic activities, along with neuroprotective, hepatoprotective or cardioprotective properties [3]. Flavonoids can act as therapeutic tool for cancer chemoprevention; research on flavonoids showed major developments in anticancer drug discoveries with potential to destroy cancer cells through apoptotic induction [4, 5]
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