English abstract
Date palm fruit (Phoenix dactylifera L.) is an endemic functional food, with great
nutritional and economic importance. Date fruit consists of carbohydrates, proteins,
vitamins, minerals, as well as dietary fibers and it is rich in phytochemicals like
carotenoids, tannins, sterols and polyphenols especially phenolic acids, isoflavons,
lignans, and flavonoids. These classes of plant derived compounds contribute to various
biological activities, e.g., anti-oxidant, anti-microbial, anti-inflammatory and anti-tumor.
Cancer is the second leading cause of death worldwide and one of the main public health
problems where the incidence and mortality rate of cancer remain high. Pancreatic cancer
has poor prognosis and high resistance to chemotherapeutic drugs due to its late diagnosis
and early metastases which make it one of the most aggressive and lethal cancers. Hence,
there is a pivotal need to find or develop a novel therapeutic approaches to treat pancreatic
cancer.
In the first stage, natural products have been extracted from Omani date fruit type
"Khalas" using aqueous and organic solvents (ethanol, n-butanol, isopropanol, acetone,
acetonitrile, dichloromethane, and ethyl acetate). The extraction yield (wt/wt%) increases
as the polarity of the extraction solvents increases, this indicate that the fruit of date palm
tree is mainly consists of polar natural products.
In the second stage, the prepared extracts were investigated for anti-fibrotic and antiproliferative activities in tumor necrosis factor (TNF) stimulated pancreatic stellate cells
(PSCs) in-vitro. Ethanol, ethyl acetate and acetone, but not water extract significantly
reduced PSCs proliferation (p<0.05). Date fruit fractions reduced fibrosis, decreased PSCs
activity and reversed the PSCs' fibrotic phenotype.
In the third stage, according to the biological activity test results, ethyl acetate and nbutanol date fruit extracts, were separated using silica gel column chromatography, based
on their polarity behavior monitored by TLC, into nine and thirteen collective fractions,
respectively. These collective fractions were subsequently, subjected to anti-proliferation
activity test on human pancreatic cancer cell lines.
In the last stage, the anti-proliferation effect of date fruit extracts has been carried out on
three different human pancreatic cancer cell lines; PT45P1, PANC-1, and SUIT-2. The
extracts demonstrated the potential to inhibit the proliferation of pancreatic cancer cells
in-vitro (p<0.05).
The findings suggest that date palm fruit appears to have chemopreventive activity
protecting from pancreatic and probably other types of cancer, and thereby date fruit
extract might be useful candidate to the pharmaceutical and nutraceutical industries in the
development of natural compound-based industrial anticancer product.