https://doi.org/10.4081/aiua.2025.14027
Anti-cancer activity of Ajwa dates extract (Phoenix Dactylifera L.) through analysis of MCL-1 levels, EGFR, and p53 expressions on apoptosis in human prostate cancer cell lines PC3: an in vitro study
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 4 August 2025
Introduction & Objectives: Prostate cancer is recognized as a global burden disease related to malignancy in men. Several fruit and plant-based supplementation have been studied to evaluate their utility for the management of prostate cancer. Ajwa dates (Phoenix Dactylifera L.) have been known to contain various beneficial compounds, which makes them a potential anti-cancer therapy. The aim of this study was to assess the effect of Ajwa dates on prostate cancer cell lines PC3 through analysis of MCL-1 levels, EGFR, and p53 expressions on apoptosis.
Materials & Methods: This study was an experimental in vitro study with post-test-only control design. Groups were divided into four: control group, abiraterone group, Ajwa dates group, and combination group (abiraterone and Ajwa dates). Viability test was conducted using the CCK-8 method to determine the inhibitory concentration (IC50) of Ajwa dates after a 72-hour incubation period of PC3 cells. The MCL-1 levels were rated using ELISA, while EGFR and p53 expressions were analyzed using immunofluorescence microscopic staining. Apoptosis was measured using fluorescence-activated cell sorting (FACS). SPSS version 25 and R-studio were used for statistical analysis.
Results: This study found the IC50 for Ajwa dates was 913.3 μg/ml. Our data indicated that Ajwa dates decrease the MCL-1 levels, EGFR and p53 expression and also induced apoptosis compared to control. Furthermore, these effects became more evident when combined with abiraterone.
Conclusions: This study demonstrates the potential of Ajwa dates as a complementary therapy for prostate cancer, but further research is still needed before clinical testing is carried out.
Downloads
Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74:229-263. DOI: https://doi.org/10.3322/caac.21834
Mirza MB, Elkady AI, Al-Attar AM, et al. Induction of apoptosis and cell cycle arrest by ethyl acetate fraction of Phoenix dactylifera L. (Ajwa dates) in prostate cancer cells. J Ethnopharmacol 2018; 218:35-44. DOI: https://doi.org/10.1016/j.jep.2018.02.030
Khan F, Ahmed F, Pushparaj PN, et al. Ajwa Date (Phoenix dactylifera L.) extract inhibits human breast adenocarcinoma (MCF7) cells in vitro by inducing apoptosis and cell cycle arrest. PLoS ONE 2016; 11:e0158963. DOI: https://doi.org/10.1371/journal.pone.0158963
Anwar S, Raut R, Alsahli MA, et al. Role of Ajwa Date fruit pulp and seed in the management of diseases through in vitro and in silico analysis. Biology 2022; 11:78. DOI: https://doi.org/10.3390/biology11010078
Assirey EAR. Nutritional composition of fruit of 10 date palm (Phoenix dactylifera L.) cultivars grown in Saudi Arabia. J Taibah Univ Sci 2015; 9:75-79. DOI: https://doi.org/10.1016/j.jtusci.2014.07.002
Azis A, Islam AA, Rasyid H, et al. The effect of flavonoid and subclasses supplementation on prostate specific antigen, hormonal parameters and prostate cancer risk: a systematic review and metaanalysis of randomized controlled trials. Arch Ital Urol Androl. 2025;97:13645. DOI: https://doi.org/10.4081/aiua.2025.13645
Shahbaz K, Asif JA, Liszen T, et al. Cytotoxic and antioxidant effects of Phoenix dactylifera L. (Ajwa Date extract) on oral squamous cell carcinoma cell line. BioMed Res Int 2022;2022:5792830. DOI: https://doi.org/10.1155/2022/5792830
He Y, Xu W, Xiao Y-T, et al. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials. Signal Transduct Target Ther 2022; 7:198. DOI: https://doi.org/10.1038/s41392-022-01042-7
Yancey D, Nelson KC, Baiz D, et al. BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in prostate cancer Cells. PLoS One 2013; 8:e74561. DOI: https://doi.org/10.1371/journal.pone.0074561
Aggarwal M, Saxena R, Asif N, et al. p53 mutant-type in human prostate cancer cells determines the sensitivity to phenethyl isothiocyanate induced growth inhibition. J Exp Clin Cancer Res CR 2019; 38:307. DOI: https://doi.org/10.1186/s13046-019-1267-z
Guérin O, Fischel JL, Ferrero J-M, et al. EGFR targeting in hormone-refractory prostate cancer: current appraisal and prospects for treatment. Pharmaceuticals 2010; 3:2238-2247. DOI: https://doi.org/10.3390/ph3072238
Fragni M, Galli D, Nardini M, et al. Abiraterone acetate exerts a cytotoxic effect in human prostate cancer cell lines. Naunyn Schmiedebergs Arch Pharmacol 2019; 392:729-742. DOI: https://doi.org/10.1007/s00210-019-01622-5
Hidayatulla F, Andhika DP, Prasetyawan W, et al. Effects of metformin and silodosin as supplementary treatments to abiraterone on human telomerase reverse transcriptase (hTERT) level in metastatic castration-resistant prostate cancer (mCRPC) cells: An in vitro study. Narra J 2024;4:e680-e680. DOI: https://doi.org/10.52225/narra.v4i1.680
Khan MA, Siddiqui S, Ahmad I, et al. Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breastcancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins. Sci Rep 2021; 11:10322. DOI: https://doi.org/10.1038/s41598-021-89420-z
Aljohani AK, Maghrabi NA, Alrehili OM, et al. Ajwa date extract (Phoenix dactylifera L.): Phytochemical analysis, antiviral activity against herpes simplex virus-I and coxsackie B4 virus, and in silico study. Saudi Med J 2025; 46:26-35. DOI: https://doi.org/10.15537/smj.2025.46.1.20240780
Situmorang PC, Ilyas S, Nugraha SE, et al. Prospects of compounds of herbal plants as anticancer agents: a comprehensive review from molecular pathways. Front Pharmacol. 2024;15:1387866. DOI: https://doi.org/10.3389/fphar.2024.1387866
Deng H, Han Y, Liu L, et al. Targeting Myeloid leukemia-1 in cancer therapy: advances and directions. J Med Chem 2024;67:5963-5998. DOI: https://doi.org/10.1021/acs.jmedchem.3c01998
Arai S, Varkaris A, Nouri M, et al. MARCH5 mediates NOXAdependent MCL1 degradation driven by kinase inhibitors and integrated stress response activation. eLife; 9:e54954. DOI: https://doi.org/10.7554/eLife.54954
Peng X-H, Karna P, Cao Z, et al. Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem 2006; 281:25903-25914. DOI: https://doi.org/10.1074/jbc.M603414200
Qin C-F, Hao K, Tian X-D, et al. Combined effects of EGFR and Hedgehog signaling pathway inhibition on the proliferation and apoptosis of pancreatic cancer cells. Oncol Rep 2012; 28:519-526. DOI: https://doi.org/10.3892/or.2012.1808
Shen Y, White E. p53-dependent apoptosis pathways. Adv Cancer Res 2001; 82:55-84. DOI: https://doi.org/10.1016/S0065-230X(01)82002-9
Grossebrummel H, Peter T, Mandelkow R, et al. Cytochrome P450 17A1 inhibitor abiraterone attenuates cellular growth of prostate cancer cells independently from androgen receptor signaling by modulation of oncogenic and apoptotic pathways. Int J Oncol 2016; 48:793-800. DOI: https://doi.org/10.3892/ijo.2015.3274
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.