The agent in their antiproliferative properties. For example,

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The induction of apoptosis is offered
to be an impressive strategy for treatment of cancer, since, cell numbers are related
to the amount of cell proliferation and death. However, malignant cells have
developed several mechanisms to resist apoptotic cell death24. Acute myeloid leukemia (AML) is a Heterogeneous  hematologic malignancy
characterized by the clonal expansion of immature myeloid blasts25. LSCs are a subpopulation of leukemic cells that indicate characteristics
of self-renewal, tumor-initiating and differentiation capacity. They are also
thought to be responsible for chemotherapy and radiotherapy resistance and the relapse
of leukemia26.There are several documents that exhibit thiosemicarbazones and
their metal complexes might be efficient in the treatment of some diseases such
as cancers27-35. The
antiproliferative effects of TSC were once particularly ascribed to the
inhibition of ribonucleotide reductase enzyme that is involved in the step of rate-limiting the synthesis
of DNA. However, the mechanism of this inhibition was initially not
demonstrated. The capability of thiosemicarbazones to chelate metal ions has
now been recognized as the main agent in their antiproliferative properties. For example, The redox activity of Fe–thiosemicarbazone
complexes is significant in their antitumor effects,
resulting in oxidative damage and the inhibition of ribonucleotide reductase. In
vivo studies demonstrate that some thiosemicarbazones indicate potential as
chemotherapeutic factors27.

The attributes
of thiosemicarbazones and their metal complexes have indicated their
adaptability to a range of applications, making them useful molecules for
further assessment as novel potential therapeutic factors aimed at cancer
therapy36. This compound has shown potent anti-proliferative and cytotoxic activities
in several human tumors, Contains A549(human lung adenocarcinoma cell line), K562, U937 (human leukemia
cell line), ECV304 (human umbilical vein endothelial cell line)11, 12, 35, 37. In a study, The antioxidant effects of the Ni–thiosemicarbazone
was investigated to test their free-radical scavenging capability. These
compounds overcome cisplatin resistance in the A549 cells and they were also
active in the HepG2 cells38.

In this study, we hypothesized that
4 -HBTC might exert oxidative stress situations-induced apoptosis in KG1a human
cancer cell line. Therefore, we have confirmed the
existence of intracellular reactive oxygen species (ROS) and of lipidic
peroxidation in KG1a cells as a consequence of treatment with nickel thiosemicarbazones. The primary ROS and
TBARS increase caused by 4 –HBTC  seem to
be limited by the
activities of GSH and antioxidant enzymes. Amazingly these intracellular scavengers seem to have no protective
effects on oxidative stress damages of 4 –HBTC, most amazingly due to Impressive effects on
cellular thiol-containing systems. This could be linked to increased cytotoxic activity
in KG1a cultures. P. Kalaivani and coworker concluded that nickel(II)
thiosemicarbazone complexes induce cytotoxicity in human lung cancer cells
(A549) via LDH and NO release into the culture medium12. Moreover, established studies report that thiosemicarbazone
complexes, could be appropriate candidates for SOD-like activity and detoxify superoxide,
by converting it to hydrogen peroxide and oxygen39, 40.

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investigation indicated that 4 –HBTC increased cellular ROS, SOD and CAT
activities in 24h and reduced activity of these enzymes after 48 and 72 h
exposure. Reduced activity of these enzymes (after
48 and 72 h) may be due to increase in the amount of apoptotic cells23. In
addition, increase in free radicals and ROS at earlier stages
(24 h) (Fig. 4) lead to increase in activity of the antioxidant enzymes (SOD
and CAT) (Fig. 5a and b). Followed by a further increase in 

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