Discussion these compounds have antitumor effect on

Discussion

In previous
studies were reported, one causes of cancer is a defect in cell cycle and
resistance to apoptosis. One of the treatments for cancer is induced the
apoptosis to cancer cells, in other words, the most anticancer drugs do their
effect by inducing apoptosis.

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One ways of
cancer therapy is chemotherapy so much effort is made to find new drugs with
less side effects and more efficacy 13. Thiosemicarbazones a class of N,
S-donor ligands 11, many applications of this family have been investigated
such as antitumor, antibacterial, antiviral, antiprotozoal and cytotoxic
effects 14.

Meta- and para- nitrobenzaldehyde thiosemicarbazones were tested on
Adenocarcinoma 755, and then showed these compounds have antitumor effect on
this cancer. Pyridine-2-carboxaldehyde thiosemicarbazone compound was found to
have antitumor effect on several lines of experimental leukemia 12. In this study,
the tests were evaluated the antitumor of the metylthiosemicarbazon complex
with Zn2+ on the K562 cell line. In morphological studies performed by optical
microscope and fluorescence microscope using acridine and orange…; it was observed that the treated
cells in this combination exhibited major morphological changes, such as
chromatin condensation and nucleation
fragmentation, in comparison to untreated cells. In this coloring, the viable
cells with a natural ???? are uniformly green with an organized structure but the cells are in early
apoptosis have bright green and show some signs of nucleation fragmentation, whereas the late
apoptotic cells exhibited orange color because they have passed EtBr. DNA
ladder assay confirmed morphological studies. DNA fragmentation is one symptom of apoptosis. Caspase-activated
DNase (CAD) is a protein that causes DNA fragmentation in nuclei during apoptosis.
In normal cells CAD is inhabited by ICAD (inhibitor of CAD) but when the process
of apoptosis starts, it can trigger the caspase cascade so caspase 3 downstream
of the cascade cleaves ICAD and inactivates its CAD-inhibitory activity. Finally, the CAD released has gone to the nucleus then degrades
chromosomal DNA. DNA fragmentation is analyzed by agarose gel electrophoresis
to confirm apoptosis induction in the metylthiosemicarbazon complex with Zn2+
treated cells Fig. The
cell cycle has five phases includes: G0 or resting, G1 or
normal growth phase, S or DNA replication phase, G2 which includes
growth phase and preparation for mitosis and M phase or mitosis . Cell cycle distribution
analysis in the K562 cells to determine the cell population using the
difference in their DNA components. In this test, each cell is stained with a
fluorescent color(PI) that interacts with DNA. It should be noted this color
can not enter the living cells so the cells are stabilized with ethanol before
staining. The cells are ready to divide increase the amount of  DNA, therefore, by increasing the
fluorescence is used to determine the percentage of cells in each phase.  In this study, the cells
were treated with metylthiosemicarbazone complex with Zn2+ that cell
death occurs through treatment of cells, as we know, one hallmark of cell death
is DNA damage. When DNA is destroyed or damaged by this compound, the
regulatory mechanisms do not allow cells to enter the next phase to repair DNA.
Before treatment with the drug, the most of cells are in G0/G1,
S, G2/M Fig.
After treatment with this
compound, cell population in G0/G1 and S phase has
decreased which represents the destruction of DNA and the cell has not been
allowed to enter these phases while the number of cells in the Sub-G1
phase has increased. It can be concluded that the drug has more effect in the Sub-G1
phase, so that    

the control cells were 5.01% in the Sub-G1 phase before
treatment but after 72 hours of treatment, this amount increased to 22.72%. It
can be concluded from this experiment that this compound induces apoptosis in K562 cell line.