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Microbes & Immunity Hyphaene thebaica honey as a multitarget therapeutic product

platform to evaluate potential therapeutic interventions.
They exhibit characteristics similar to those of aggressive
breast cancer phenotypes. Notably, no cytotoxic effects
were observed across all tested concentrations. DH
exhibited a modest yet significant cytostatic activity
on MDA cells. The most pronounced cytostatic effects
were noted at concentrations of 4 mg/mL and 2 mg/mL,
leading to a reduction in cell viability by 25% and 20%,
respectively, compared to untreated control cells. These
findings are consistent with prior studies, underscoring
that the influence of honey can vary based on its type. 65-68
Furthermore, our results corroborate numerous studies Figure 3. Effect of honey samples on MDA cell migration. The results
that have highlighted the cytostatic properties of honey reflect the extent of wound closure after 24 and 48 h of treatment with
on diverse cancer cells, suggesting that these effects honey samples. Each data point was determined based on the initial
are modulated by the phenolic content. 65-68 Recent wound size at time 0 h and was normalized to the untreated control, which
findings by Imtara et al. revealed the cytotoxic effects of was set as 100%. Data represent the mean ± SD from three independent
66
various honeys from Morocco and Palestine on human experiments conducted in triplicate. *P < 0.05 compared to the untreated
control.
colon adenocarcinoma (HCT-116) and breast cancer Abbreviation: DH: Doum honey.
(MCF-7) cell lines. Their study highlighted a strong positive
correlation between the concentration of antioxidant These findings are consistent with previous studies
components such as phenols, flavonoids, and flavonols and that have reported the inhibitory effects of various honey
the cytostatic effects observed in MCF-7 cells. In addition, types and isolated phytochemicals, such as resveratrol,
an inverse relationship was identified between the levels kaempferol, and epigallocatechin-3-gallate, on the
of syringic and tannic acids and the cytostatic activity in migration of colorectal cancer and oral squamous cell
HCT-116 cells. Similarly, research has demonstrated the carcinoma cells. To the best of our knowledge, this
cytotoxic effects of Sardinian STH honey and Manuka is the first study to demonstrate the antimetastatic
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honey from New Zealand on HCT-116 and metastatic properties of Palestinian honey on MDA breast cancer
69
colon epithelial adenocarcinoma cells, with reduced cell lines. 72-74 Metastasis, the most lethal aspect of
cytotoxicity observed in non-cancerous cells. Furthermore, cancer, involves intricate processes and a wide array of
75
Chinese jujube honey was found to exert cytotoxic effects molecules, including matrix metalloproteinases (MMPs),
76
on HepG2 liver cancer cells. 69,70 integrins, cadherins, plasminogen activators, PI3Ks, small
GTPases (e.g., Rho, Rac, Cdc42), phospholipase C, and
3.4. Effect of honey samples on cell migration of focal adhesion kinases. Although the effects of honey on
MDA cells
cancer metastasis remain underexplored, an in vivo study
Cancer is characterized not only by the unregulated and using wildflower honey from Croatia revealed a significant
accelerated proliferation of cells but also by the invasive reduction in metastasis when administered before tumor
and metastatic nature of these proliferating cells. It is cell inoculation in CBA mice and Y59 rats. 77
well recognized that the tendency of breast cancer cells Beyond the cytostatic effects of honey samples, the
to metastasize to other tissues significantly increases the suppression of MMPs is probably a mechanism behind
mortality risk. 71
their beneficial properties. MMPs are proteases critical for
Here, we performed a scratch assay to assess the impact extracellular matrix degradation and are highly expressed
of DH, administered at a dose of 4 mg/mL, on migration in metastatic cells. Gallic acid, a phenolic compound,
78
of MDA cells. As illustrated in Figure 3, treatment with has been shown to reduce the gelatinolytic activity of
DH significantly reduced the migration rate of MDA MMP-2 and MMP-9, potentially via modulation of the
cells compared to the untreated controls (P < 0.05). This nuclear factor kappa B (NF-κB) pathway. Furthermore,
63
reduction in tumor cell migration may partly result several studies suggest that honey can inhibit both the
from the DH’s cytostatic properties, as evidenced by its expression and nuclear translocation of NF-κB in vivo and
inhibition of cell migration and its cytostatic effects on in vitro settings. 79-81 Honey has also been demonstrated to
MDA cells (Figure 2). Notably, the more pronounced decrease the enzymatic activity of MMP-2 and MMP-9.
82
suppression of cell migration relative to its cytostatic For example, Fir honey was found to inhibit human
effects suggests the involvement of additional cellular and keratinocyte migration by downregulating MMP-9
molecular mechanisms underlying DH’s beneficial effects. expression. 82,83 Similarly, quercetin, a flavonoid present

Volume 2 Issue 1 (2025) 84 doi: 10.36922/mi.4994