Ajwa Date (Phoenix dactylifera L.) Extract Inhibits Human Breast Adenocarcinoma (MCF7) Cells In Vitro by Inducing Apoptosis and Cell Cycle Arrest

Khan, Fazal; Ahmed, Farid; Pushparaj, Peter Natesan; Abuzenadah, Adel M.; Kumosani, Taha A.; Barbour, Elie K.; Al-Qahtani, Mohammed Hussein; Gauthaman, Kalamegam

doi:10.1371/journal.pone.0158963

Cited by 68 publications

(58 citation statements)

References 41 publications

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“…This data suggests that ADPE treatment pushes the cancer cells into late apoptosis stage. A previous study has also reported that methanolic extract of Ajwa dates induces apoptosis in breast cancer MCF-7 cells by increasing the percentage of cells in late apoptosis [20]. DNA fragmentation data also confirmed the apoptosis-inducing efficacy of ADPE against MDA-MB-231 cells.…”

Section: Discussionsupporting

confidence: 67%

Induction of apoptosis by phytochemicals of Ajwa dates extract in human triple-negative breast cancer cells by triggering cell cycle arrest, inhibiting Akt/mTOR signaling and modulating downstream Bcl-2 family of proteins

Khan¹,

Siddiqui²,

Ahmad³

et al. 2020

Preprint

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Background:Ajwa date (Phoenix dactylifera L.) has been described in traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remain to be scientifically validated. In the present study, we evaluated the anticancer effects of the ethanolic extract of Ajwa Dates pulp on human triple-negative breast cancer MDA-MB-231 cells. MethodsAjwa Dates Pulp Extract (ADPE) was phytochemically characterized using high performance liquid chromatography coupled with mass spectrometry (LC-MS). The in vitro cytotoxicity of ADPE at various concentrations viz. 10, 12, 15, 18, 20, 22 and 25 mg/mL were evaluated against MDA-MB-231 and MCF-7 cells at 24 and 48 h. The apoptosis effect was examined by Hoechst 33342 and AO/PI-double-stain using fluorescence microscopy. The proportion of apoptotic cells, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) and cell cycle phase distribution were estimated using flow cytometry. Apoptosis-related protein expression was determined using western blot analysis. ResultsLC-MS analysis showed that ADPE contained phytocomponents belonging to chemical classes such as carbohydrates, phenolics, flavonoids and terpenoids. Phase contrast microscopy analysis revealed various morphological variations in ADPE treated cells. MTT assay demonstrated statistically significant dose- and time-dependent inhibitions of MDA-MB-231 cells with a half-maximal inhibitory concentration 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, Ajwa date extract prompted ROS induced alterations in MMP in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. In addition, ADPE upregulates p53, Bax and cleaved caspase-3, thereby leading to downregulation of bcl-2 protein and Akt/mTOR pathway. ConclusionsThe results of the present study indicate that ADPE exerts significant anticancer effects on MDA-MB-231 cells via the induction of apoptosis and suppression of AKT/mTOR signaling pathway. Therefore, ADPE has the potential to be used as an adjunct to the main line of treatment against breast cancer and can be further studied as a potential lead in breast cancer treatment.

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Section: Discussionsupporting

confidence: 67%

Induction of apoptosis by phytochemicals of Ajwa dates extract in human triple-negative breast cancer cells by triggering cell cycle arrest, inhibiting Akt/mTOR signaling and modulating downstream Bcl-2 family of proteins

Khan¹,

Siddiqui²,

Ahmad³

et al. 2020

Preprint

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“…However, the most attention-grabbing effects are highlighted for its activities against various kinds of cancers. Its anticancerous, antiproliferative, and antiangiogenic activities are reported against mammary cancer [11], colon cancer, [26] and breast cancers [27].…”

Section: Introductionmentioning

confidence: 99%

Phoenix dactyliferaProtects against Doxorubicin-Induced Cardiotoxicity and Nephrotoxicity

Wang

Chao

Ahmad

et al. 2019

Cardiology Research and Practice

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Doxorubicin (DOX) is an important anticancer drug used widely in the treatment of leukemia and lymphoma. The suitability of DOX is enhanced by its high therapeutic index, but its potential to cause cardiotoxicity and nephrotoxicity remains a prime concern in anticancer therapeutics. This study is designed to determine the effect of Phoenix dactylifera extract (PDE) on DOX-induced cardiotoxicity and nephrotoxicity. Experimental rats were divided into four groups, receiving normal saline 4 ml/kg, DOX alone, and crude extract of PDE at doses of 1 g/kg and 1.5 g/kg in the presence of DOX, respectively, for 21 days. Cardiac enzymes and serum and urinary sodium and potassium levels were evaluated which were analyzed statistically by using one-way ANOVA. Subsequently, DOX initiated changes in the level of cardiac markers CK-MB, LDH, and troponin I, which were notably reversed by PDE. PDE was also effective against serum and urinary sodium and urinary potassium and protected against DOX-induced nephrotoxicity. Groups treated with different doses of PDE showed marked decrease in levels of cardiac and renal markers. The study concluded that the PDE extract possesses protective effects against DOX-induced cardiotoxicity and nephrotoxicity.

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“…Natural or herbal medicines are often used as alternative forms of chemotherapy, due to low mortality and side effects (10). Currently, novel anticancer agents from natural products have become increasingly popular (11). In the history of Traditional Chinese Medicine (TCM), medicinal plants and their extracts have been used to treat various diseases.…”

Section: Introductionmentioning

confidence: 99%

Sodium cantharidinate suppresses human osteosarcoma MG‑63 cell proliferation and induces cell cycle arrest by inhibition of PI3K/AKT activation

et al. 2018

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The function and mechanism of sodium cantharidininate (SC) underlying its suppression of human osteosarcoma (OS) MG-63 cells were investigated for the first time in the present study. MG-63 cell proliferation was determined by WST-1 assay post SC treatment at 0, 12, 24, 48 and 72 h. The results showed that SC effectively inhibited MG-63 cell proliferation and induced cell cycle arrest at the G0/G1 phase in a dose-dependent manner. Western blotting revealed that SC induced MG-63 cell cycle arrest at the G0/G1 phase by means of inhibition of cyclin D1, CDK4 and CDK6 expression.

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Ajwa Date (Phoenix dactylifera L.) Extract Inhibits Human Breast Adenocarcinoma (MCF7) Cells In Vitro by Inducing Apoptosis and Cell Cycle Arrest

Cited by 68 publications

References 41 publications

Induction of apoptosis by phytochemicals of Ajwa dates extract in human triple-negative breast cancer cells by triggering cell cycle arrest, inhibiting Akt/mTOR signaling and modulating downstream Bcl-2 family of proteins

Induction of apoptosis by phytochemicals of Ajwa dates extract in human triple-negative breast cancer cells by triggering cell cycle arrest, inhibiting Akt/mTOR signaling and modulating downstream Bcl-2 family of proteins

Phoenix dactyliferaProtects against Doxorubicin-Induced Cardiotoxicity and Nephrotoxicity

Sodium cantharidinate suppresses human osteosarcoma MG‑63 cell proliferation and induces cell cycle arrest by inhibition of PI3K/AKT activation

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