الفهرس 
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Abstract
We summarize whether B. nigra seeds extract affect the proliferation, migration and invasion
of A549 and H1299 lung cancer cells.
The chemotherapeutic potential of B. nigra extract has been assessed by treating A549 and
H1299 cells. The IC
50
values are found to be 32.02 and 25.38 μg/mL against the A549 and H1299
cell lines, respectively. Accordingly, B. nigra extract showed substantial growth-inhibitory effect
on A549 and H1299 cells.
The kinetic activity of caspase-3 was increased in B. nigra-treated A549 and H1299 NSCLC
cells in a time-dependent manner. These findings indicate that B. nigra extract has the ability to
induce apoptosis of A549 and H1299 cells.
DNA damage induced by replication stress leads to collapsed replication forks. The current
study showed that B. nigra alone or in combination with CPT induced hyperactivation of
ATM/ATR-mediated DDR as indicated by elevated level of γH2AX as well as increased pATM,
checkpoint kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) when compared to CPT treatment
alone. Additionally, the extract alone or in combination with CPT enhanced the cyclin B1 and Bid
expressions when compared to control.
The cell cycle analysis indicates that both A549 and H1299 cells were significantly delayed
and arrested at S and G2/M transition after 24h treatment with B. nigra extract in a concentrationdependent
manner.
Concerning the potential effect of B. nigra extract on EMT, B. nigra extract significantly
suppressed the migration and reduced the wound closure of A549 cells after 15 h in a
concentration-dependent manner. These results confirm the suppressive effect of B. nigra on A549
and H1299 cells migration and Invasion and confirmed that the extract significantly suppressed
the invasive ability of cancer cells when compared to corresponding control.
In regard the associated genes to EMT, the qPCR confirmed that B. nigra-treated cells
exhibited decreased mRNA levels of MMP2, MMP9 and Snail, and increased mRNA level of Ecadherin
in a concentration-dependent manner when compared to control for both A549 and
H1299 cells. Moreover, B. nigra extract downregulated the protein expression of Snail and
upregulated E-cadherin protein expression in a concentration-dependent manner for A549 and
H1299 cells.