Ajwa Date (Phoenix dactylifera L.) as a Potential Anticancer Agent against Cervical Cancer: A Systematic Review of Cytotoxicity and Apoptosis-Related Mechanisms

Abstract

Cervical cancer remains a major global health problem, particularly in low- and middle-income countries. Limitations associated with conventional therapies, including toxicity and treatment resistance, have stimulated interest in natural products with potential anticancer activity. Ajwa date (Phoenix dactylifera L.) is rich in polyphenols, flavonoids, phenolic acids, and other bioactive constituents that may modulate cancer-related signalling pathways. This systematic review aimed to synthesise evidence on the cytotoxic and apoptosis-related effects of Ajwa date extracts and to evaluate their mechanistic relevance to cervical cancer. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, ScienceDirect, and the Cochrane Library from database inception to August 2026, following PRISMA 2020 guidelines. Studies reporting cytotoxicity and/or apoptosis-related outcomes of Ajwa or closely related Phoenix dactylifera extracts in cancer models were included. Data were narratively synthesised because of substantial heterogeneity in extract preparation, cell models, exposure conditions, and analytical methods. Of 312 identified records, 18 primary studies fulfilled the eligibility criteria. Most evidence originated from breast, hepatocellular, oral squamous, and prostate cancer models, whereas direct evidence in cervical cancer cell lines remained limited. Ajwa-derived preparations generally demonstrated dose- and time-dependent reductions in cancer-cell viability. The predominant mechanistic pattern involved increased intracellular oxidative stress, loss of mitochondrial membrane potential, increased Bax/Bcl-2 ratio, caspase activation, PARP cleavage, and cell-cycle arrest. Some studies also reported down-modulation of AKT/mTOR, EGFR, and other survival-related pathways. Seed or pit-derived extracts frequently showed greater cytotoxic potency than pulp-derived preparations and, in several studies, demonstrated lower toxicity toward normal cells. Ajwa date extracts exhibit consistent cytotoxic and pro-apoptotic activity across several cancer models and show biological plausibility as potential candidates for cervical cancer research. However, direct evidence in HeLa, SiHa, and CaSki cells remains insufficient. Standardised phytochemical characterisation, comparative studies across cervical cancer cell lines, selectivity testing, and well-designed in vivo investigations are required before therapeutic or clinical implications can be established.