Abstract
Cancer remains one of the most devastating diseases affecting people worldwide. For
decades, it has been established that currently available cancer treatments have limitations,
therefore the ongoing quest for alternative medicines that can eliminate the disease, thereby
improving the lives of many people now affected by it. Cancer has risen to become the world's
second leading cause of death, after cardiovascular diseases, and it is posing an impediment
to greater life expectancy. With 19.3 million cancer diagnoses and over 10 million deaths
estimated in 2020 worldwide, it is critical to tackle cancer, which is claiming more lives as the
years pass. The present therapies have limitations owing to cancer's resistance to therapy,
ability to metastasize to other areas of the body, and recurrence. Many plants contain
medicinal properties and can therefore be exploited in the quest for innovative, efficient, and
significantly affordable cancer treatments. The main objectives of this study were to isolate
bioactive compounds from Erythrina abyssinica, and to test their cytotoxicity on various types
of cancer cells, and a normal cell line to test for adverse effects. Once bioactive compounds
were established, their anticancer activities were studied by conducting a series of cytotoxic,
apoptotic, wound healing and gene expression analyses. Two flavonoid compounds were
isolated and were established through spectroscopic analysis to be 5-methoxyjamaicin and
derrone. Both compounds were found to be cytotoxic against PaCa-2, ME-180 and A375
cancer cells, and exhibited negligible cytotoxicity on HEK293 normal cells. It was proposed
that these compounds utilized the intrinsic apoptotic pathway to exhibit their apoptosis
inducing cytotoxic effect in cervical and melanoma cancer cells, whereas the exact pathway
in pancreatic cancer cells could not be determined. Apoptosis was characterized
morphologically by cell shrinkage, chromatin condensation, loss of epithelial morphology,
nuclear fragmentation, and loss of cell-to-cell interactions. Furthermore, high caspase levels
were observed for cells treated with the compounds, and these cells were inhibited from
migrating, thus indicating an inhibition of metastasis. The aim of the study was to conjugate
the flavonoids to metallic nanoparticles to test if the inhibition of cell proliferation would be
enhanced. The findings of this study demonstrated that, when 5-methoxyjamaicin and derrone
were conjugated to silver nanoparticles, their cytotoxic activity was much greater than the
cytotoxicity of the non-conjugated natural compounds but proved damaging to healthy normal
cells. Therefore, the non-conjugated natural 5-methoxyjamaicin and derrone may serve as
promising anticancer flavonoids. Further research is needed to identify and understand other
biological processes and cancer-associated genes that may be impacted by these
compounds, as well as to examine how to improve the delivery of these specific compounds
without eliciting adverse effects on normal cells.
Keywords: cancer, flavonoids, silver nanoparticles, secondary metabolites, Erythrina abyssinica