الفهرس 
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Abstract
Globally, breast cancer (BC) is the most commonly diagnosed cancer and the major
cause of cancer-related death among females. It has become a global health concern because
it was depicted that over 7.8 million women were diagnosed by BC in 2021. The global
burden of BC is increasing every year in both developing and developed countries. Due to
poor responses to chemotherapy and aggressive behavior, there is an urgent need for a
therapeutic strategy to meet the present difficulties associated with BC. In order to combat
developing drug resistance or adverse effects, natural items should be evaluated as potential
therapeutic choices with less side effects against such disease. Therefore, there is a need for
rapid BC therapy with no adverse effects. Consequently, in this investigation, we mainly
concentrated on natural algal extracts [Sarconema filiforme (S. filiforme) and Laurencia
obtusa (L. obtusa)] and the antimicrobial peptide (AMP) Smp43 isolated from scorpion
venom on human breast cancer cell lines [triple negative (MDA-MB-231) and luminal A
(MCF-7)] and identify their mechanism of actions.
The main objectives of this study are:
1. Natural algal extracts [Sarconema filiforme (S. filiforme) and Laurencia obtusa (L.
obtusa)] were structurally characterize and assess cytotoxicity of both ethanolic and
chloroform extracts of S. filiforme and L. obtusa red seaweed collected from the Suez Canal
coasts, Egypt. Extracts of S. filiforme and L. obtusa were prepared and characterized using
GC/MS analysis and MTT assay was used to examine their toxicity against different cancer
cell lines including to human breast cancer (MCF-7 and MDA-MB-231 cells) and lung
adenocarcinoma (A549 cells) cell lines. Using GC/MS analysis, a total of 34 and 29 different
compounds were identified in the extracts of S. filiforme and L. obtusa, respectively. The
most abundant constituents in both algae species are cholesterol and diisooctyl phthalate. The
in vitro assays revealed a mild to moderate cytotoxicity of the two crude extracts of both
species on MCF-7, MDA-MB-231, and A549 cells.
2. Antimicrobial peptide (AMP) Smp43 isolated from scorpion venom has been used
to estimate the cytotoxicity and the molecular mechanisms of Smp43 in human breast cancer
cell lines (MDA-MB-231 and MCF-7). Cells were treated with Smp43 and various assays
have been performed including MTT assay, apoptosis assay (Annexin V/PI staining), cell
cycle analysis, DNA fragmentation by DPA and agarose gel electrophoresis, and wound healing assay. In addition, apoptosis-related gene expression levels were determined by qRTPCR
while the expression levels of cell proliferation/migration/invasion-related genes were
determined by western blotting. Treatment with Smp43 inhibited cell proliferation,
migration, and metastasis, but it induced cell apoptosis as observed by DNA fragmentation
and Annexin V/PI analysis. Further molecular mechanism studies showed that bax, p53,
caspase 7, and caspase 9 expression levels were found to be up regulated in both treated cell
lines. On the other hand, bcl-2, ki67, PCNA, laminin-5, and upA expression levels
significantly downregulated in both treated cell lines. These findings were also validated by
ELISA test of cytochrome C, MMP9, and VEGF. The present results revealed that
proliferation of breast cancer cells is dramatically reduced in vitro by Smp43 through
apoptosis induction and migration/invasion inhibition. Generally, our results shed a light on
the anticancer action of Smp43, which could eventually be used to create effective
therapeutic medicines for treating breast cancer.