The polyphenol/saponin-rich Rhus tripartita extract has an apoptotic effect on THP-1 cells through the PI3K/AKT/mTOR signaling pathway

Abstract

Background 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. 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. Methods After 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. Results Analysis 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. Conclusion Rhus 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.

Four new triterpene saponins from Cephalaria speciosa and their potent cytotoxic and immunomodulatory activities

“…These results demonstrated that bisdesmosidic compounds ( 2–4 ) did not show any cytotoxic activity while following monodesmosidic compounds ( 1 , 2a , 3a , and 4a ) have cytotoxic effect on cancerous cell lines. In literature, as a similar study Tlili et al 31 , who identified the biochemical profiles of the major compounds found in plant leaf extract and examined its anti-leukemic potential against acute monocytic leukemia (AML) THP-1 cells. They proved that the mTOR pathway may be involved in cell cycle inhibition and apoptosis induction caused by saponin.…”

An insight into PI3k/Akt pathway and associated protein–protein interactions in metabolic syndrome: A recent update

“…PI3K/Akt intracellular signaling pathway is involved in many aspects of cellular survival and growth, in physiological as well as pathological conditions. Disruption of the PI3K/Akt pathway contributes to multiple cardiovascular diseases, such as type II diabetes, insulin resistance, hypertension, and hyperlipidemia 18–24 . PI3K signaling can be activated following a wide range of cues emanating from the plasma membrane, such as integrins, G‐protein coupled receptors (GPCR), immune receptors, receptor tyrosine kinases, and small Ras‐related GTPases.…”

“…Disruption of the PI3K/Akt pathway contributes to multiple cardiovascular diseases, such as type II diabetes, insulin resistance, hypertension, and hyperlipidemia. [18][19][20][21][22][23][24] PI3K signaling can be activated following a wide range of cues emanating from the plasma membrane, such as integrins, G-protein coupled receptors (GPCR), immune receptors, receptor tyrosine kinases, and small Rasrelated GTPases. The binding of ligands to cellmembrane receptors (receptor tyrosine kinases or GPCR) activates PI3K.…”

Optimization of Total Saponin Extraction from Polyscias fruticosa Roots Using the Ultrasonic-Assisted Method and Response Surface Methodology

“…Many naturally occurring anti-cancer agents have been extracted with high efficiency and recovery by UAE, such as mangiferin from Mangifera indica L. [22], taxol from Taxus mairei [23], flavonoids from Celastrus hindsii [24], and tannins and polyphenols from Pistacia lentiscus [25]. The extraction of saponins with anti-cancer activity from plants such as Curcuma angustifolia, Psidium guajava, Rhus tripartite, and Calotropis gigantea, have still not been reported from P. fruticose [26][27][28][29]. Simultaneously, response surface methodology (RSM) is also commonly employed for extraction optimization of plant-based compounds and analysis of the interactions between different factors as well as the effect of each factor on the response values.…”