الفهرس 
Review
In Vivo ExperimentsOnly 14 pages are availabe for public view
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Abstract
Cancer is a general term for a group of diseases that affect any part of
the body. It is one of the leading causes of mortality worldwide with an
estimation of 9.6 million deaths in 2018. Cancer arises from the
transformation of normal cells into tumor cells through multiple
mutations in a multistage process,leading to the formation of a
malignant tumor from a pre-cancerous lesion.
Liver cancer is one of the main causes of cancer-related death in the
world. Hepatocellular carcinoma (HCC) accounts for between 85% and
90% of primary liver cancer.
Doxorubicin was commonly used in the treatment of HCC, however,
its use has been limited by its serious side effects especially
cardiotoxicity and the development of cellular resistance. As
doxorubicin is a mitochondrial toxin its mitochondrial damage is
central to Dox-induced cardiac dysfunction and cell death. An
increasing number of studies had focused on finding new drugs to
overcome the cardiotoxicity of doxorubicin.
Organogermanium has been used as a dietary supplement and its
therapeutic attributes include fighting cancer and improving the
immune system. Its compounds are powerful antioxidants that showed
great effect to protect against cancer.
Vitamin C which is a water-soluble vitamin induces death of various
types of cancer cells. A growing number of studies have demonstrated that millimolar concentrations of pharmacological vitamin C can kill
cancer cells in vitro and slow tumor growth in vivo.
According to this knowledge recent studies investigate the antitumor
activity of newly synthesized organogermanium complexes alone and
when combined with ascorbic acid. The present study was carried in
vitro on HEPG2 cell line and in vivo on Ehrlich ascites bearing mice,
and the following parameters were tested:
In vitro
1. Evaluating the cytotoxicity of organogermanium compounds
and calculating the IC50% value.
2. Analyzing the effect of combination of four Ge compounds and
ascorbic acid on HEPG2 cell line using doxorubicin as positive
control
3. Investigating the biological activity of the four Ge complexes
alone and combined with ascorbic acid by measuring apoptotic
and cell proliferation markers this included Ki67, bcl2 and
caspase 3.
In vivo
Two complexes were chosen for in vivo assessment
1. Ehrlich ascites bearing mice were treated with the two of the
Ge compounds alone and combined with ascorbic acid.
Doxorubicin was used as positive control.
2. The mice survival rate was estimated. The ascites volume and
the mice weights were measured.3. IL2 and IL6 level were tested in mice.
Findings of the present study can be summarized as follow:
In vitro results:
1. The newly synthesized Ge-compounds exhibited higher
cytotoxicity on tumor cells with lower side effects on normal
cells.
2. Ge-arginine complex induces apoptosis and cell cycle arrest in
the HEPG2 cell lines. Its effect, alone or combined with ascorbic
acid, on cancer HEPG2 is superior to that of the well
documented anticancer drug doxorubicin.
3. Ge-adenosine complex has an antitumor activity, which may
work through activation of apoptosis by intrinsic pathway. The
combination of Ge-(adenosine) with ascorbic acid ameliorated
the effect of the compound on caspase3 and bcl-2 expression
when compared to the complex alone.
4. Ge (gly-his)is was more effective than doxorubicin in down
regulating the level of Ki 67,and up regulating caspase 3,but its
effect on bcl-2 was weaker than that of doxorubicin.
5. Ge- (lauryl amine)when combined with vitamin C lowers bcl-2,
and consequently inhibits cancer proliferation and increases its
apoptosis, more effectively than the other organogermanium
complexes included in the present study.In vivo results:
1. The addition of ascorbic acid to Ge-(arginine), compensated its
toxicity, and 100% of the EAC bearing mice survived the
experiment. Meanwhile, the addition of ascorbic acid to
doxorubicin or Ge-(adenosine) increased their toxicity to the
EAC bearing mice, causing a decrease in survival to 62.5% and
50% respectively.
2. Both groups treated with doxorubicin; alone and combined with
ascorbic acid, showed no ascites at the end of the experiment.
However, the organogermanium treated groups showed a
moderate decrease (around 50%) in the ascites volume compared
to the untreated group.
3. Both Ge-arginine and Ge-adenosine could decrease the
progression of cancer, by lowering the IL-2 level, when
administered without the ascorbic acid. On the other hand,
doxorubicin combined with ascorbic acid is more powerful in
reducing IL-2 level.
4. IL-6 was down regulated after the treatment with the Ge
complexes, which indicates a good response to the treatment.