Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins

Abstract

Ajwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC–MS) and investigated anticancer effects against MDA-MB-231 cells. LC–MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.

Anticancer potential of Phoenix dactylifera L. seed extract in human cancer cells and pro-apoptotic effects mediated through caspase-3 dependent pathway in human breast cancer MDA-MB-231 cells: an in vitro and in silico investigation

“…Previous studies have confirmed the anticancer activities of both bioactive agents against different human cancer cell lines [ 62 – 64 ]. In our recent publications, the pulp extract of Ajwa dates has shown IC 50 values of 20.03 and 16.78 mg/mL at 24 and 48 h periods, respectively, against human liver cancer HepG2 cells and IC 50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively against TNBC MDA-MB-231 cells [ 23 , 65 ]. While the active components of Ajwa date pulp extract in the previous study was β-D-glucan (a polysaccharide), rutin and quercetin were the active phytoconstituents identified in PDSE.…”

Role of Ajwa Date Fruit Pulp and Seed in the Management of Diseases through In Vitro and In Silico Analysis

“…LC–MS analysis conducted by Khan and coworkers revealed the presence of various phytocomponents in Ajwa date pulp extract belonging to classes such as carbohydrates, phenolics, flavonoids, and terpenoids. Maltose, catechin, myricetin, quercetin, β-sitoserol, digalacturonic acid, chlorogenic acid, and β-carotene were found to be major molecules [ 37 ]. Moreover, the LC-linear ion quadrupole mass spectrometric analysis (LC-MS and LC-MS/MS tandem mass spectrometry) analysis revealed the presence of 3,30-di-O-methyl ellagic acid, 7-methoxyquercetin-O-hexose isomers, caffeic acid, ferulic acid, isomers of quercetin-rutinoside, kaempferol methylether, p-hydroxybenzoic acid, phytol, punicalagin, and quercetin-3-O-glucoside (isoquercitrin) in Ajwa [ 38 ].…”

P53-Related Anticancer Activities of Drimia calcarata Bulb Extracts Against Lung Cancer

“…In the p53 -mutant H1573 ( Figures 4E,F ) and p53 -mutant H1437 ( Figures 5E,F ) AO/EB staining revealed similar stained cells (green), reduction in cancer cell number and also feature of apoptosis like cell shrinkage and nuclei fragmentation were observed following treatment with ME and WE. For preliminary confirmation of apoptotic/necrotic cell death, AO/EB staining has been used in several studies ( Rajavel et al, 2017 ; Suganya et al, 2019 ; Khan et al, 2021 ). This results provide morphological proof that the Drimia calcarata extracts induce apoptosis and inhibit cell growth of NSCLC cell lines.…”