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

BMC Complementary Medicine and Therapies

Anca Macovei¹  Daniela Buonocore¹  Maurizia Dossena¹  Enrico Doria¹  Andrea Pagano¹  Manuela Verri¹  Anita Lombardi²  Manuela Lanzafame²  Hajer Tlili³  Mohamed Neffati³  Abdelkarim Ben Arfa³  Hanen Najjaa³ 

[1] Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, via Ferrata 9, 27100, Pavia, Italy;Institute of Molecular Genetics IGM CNR, Pavia, Italy;Laboratory of Pastoral Ecosystems and Valorization of Spontaneous Plants and Microorganisms, Institute of Arid Regions (IRA), Tunis, Medenine, Tunisia;

关键词: Plant extracts;    Medicinal plants;    Rhus tripartita;    mTOR pathway;    Anticancer properties;    Apoptosis;    Leukaemia;   

DOI  :  10.1186/s12906-021-03328-9

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY