Abstract
Organic fractions and extracts of willow (Salix safsaf) leaves, produced by sequential solvent extraction as well as infusion and decoction, exhibited anticancer potencies in four cancerous cell lines, including breast (MCF-7), colorectal (HCT-116), cervical (HeLa) and liver (HepG2). Results of the MTT assay revealed that chloroform (CHCl3) and ethyl acetate (EtOAc)-soluble fractions exhibited specific anticancer activities as marginal toxicities were observed against two non-cancerous control cell lines (BJ-1 and MCF-12). Ultra-high-resolution mass spectrometry Q-Exactive™ HF Hybrid Quadrupole-Orbitrap™ coupled with liquid chromatography (UHPLC) indicated that both extracts are enriched in features belonging to major phenolic and purine derivatives. Fluorescence-activated cell sorter analysis (FACS), employing annexin V-FITC/PI double staining indicated that the observed cytotoxic potency was mediated via apoptosis. FACS analysis, monitoring the increase in fluorescence signal, associated with oxidation of DCFH to DCF, indicated that the mechanism of apoptosis is independent of reactive oxygen species (ROS). Results of immunoblotting and RT-qPCR assays showed that treatment with organic fractions under investigation resulted in significant up-regulation of pro-apoptotic protein and mRNA markers for Caspase-3, p53 and Bax, whereas it resulted in a significant reduction in amounts of both protein and mRNA of the anti-apoptotic marker Bcl-2. FACS analysis also indicated that pre-treatment and co-treatment of human amniotic epithelial (WISH) cells exposed to the ROS H2O2 with EtOAc fraction provide a cytoprotective and antioxidant capacity against generated oxidative stress. In conclusion, our findings highlight the importance of natural phenolic and flavonoid compounds with unparalleled and unique antioxidant and anticancer properties.
Highlights
Despite significant progress made towards discovery of potent chemotherapeutic agents, cancer remains an aggressive and devastating disease
natural products (NPs) are promising for developing novel chemical entities (NCEs) in the fight against cancer as they have been reported to be rich in bioactive, secondary metabolites such as phenolic and flavonoid compounds [9,22,23]
The current study was designed to further explore the spectrum and modes-of-action of anticancer potential mediated by organic fractions and extracts of willow leaves, against four selected types of cancer cells, MCF-7, HCT-116, HeLa and HepG2
Summary
Despite significant progress made towards discovery of potent chemotherapeutic agents, cancer remains an aggressive and devastating disease. Cancer is ranked as the first cause of mortalities in 21 states of the United States of America, with estimated new cases and fatalities in 2018 of around 1.7 million and 600,000, respectively [2]. Anticancer activities of several novel NP and NP-derived drug pharmacophores have been tested at both pre-clinical and clinical (Phases I, II and III) stages, offering a bright prospect for future registration and approval of several of them. Many of these candidate drugs have not made it to clinical trials, or their clinical trials have been halted or discontinued. Plant-derived NPs from roots, bark and leaves of terrestrial plants are fundamental to CAM-based cancer therapeutic strategies in several countries
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