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Table 3: Effect of DADS, at various concentrations, on
percent inhibition of EAC-cell viability in vitro
Compound Percentage of inhibition of cell viability (μg/mL)
0 6.25 12.5 25 50 100
DADS 0 16.5 35 70 90 100
IC50: 19.500 μg/mL. EAC: Ehrlich ascites carcinoma; DADS: diallyl disulfi de
cytotoxicity effects of DADS against EAC in vivo and in vitro. In
addition, the apoptogenic effects of this agent were assessed
by investigating the histological changes and measuring
some apoptotic and anti-apoptotic mediators by imaging and
semi-quantitative analysis of immunohistochemically stained
sections of EAC-cells.
a
The current in vivo study revealed that DADS has a potential
antiproliferative and cytotoxicity effect against EAC
(a transplantable neoplasia from a malignant epithelium that
corresponds to mammary adenocarcinoma) in EAC-bearing
female mice. [14,21] This activity was confirmed by a significant
decrease in EAC-aliquot volume and total and alive EAC-cell
number, and a tremendous increase in dead EAC-cell
count and percent as a result of treatment with DADS in
comparison to a vehicle. The anti-tumor cytotoxicity of DADS
was associated with an improved survival and increased
the life span of EAC-bearing mice. The plasma and Ehrlich
ascites tumor marker, sialic acid, was significantly decreased
in EAC-bearing mice treated with DADS as compared
b to EAC-bearing control mice. These in vivo results were
supported by in vitro study which indicated that DADS induced
unexpected anti-proliferative and anti-tumor cytotoxicity
effects against EAC-cells.
In concurrence with the present results, the sialic acid, the
component of glycoproteins and glycolipids that constitute
the cell surface, was reported to be shed or secreted by tumor
cells leading to its increased level in blood of humans with
[22]
cancer and in animal cancer models. The sialic acid level
in serum and plasma was reportedly decreased in C57BL/6
[23]
mice lung metastasis of B16F-10 melanoma cells and in
alloxan diabetic rats, respectively. The anti-proliferative
[24]
and apoptotic effects of DADS derived from Allium sativum
in different carcinomas both in vivo and in vitro were also
c elucidated by various authors. [25-27]
Figure 4: Data of image analysis of immunohistochemically stained EAC-sections
showing (a) area in pixels, (b) percent area, and (c) the intensity of yellowish brown The histological findings of this study indicated that many
color of immunoreactive Bcl-2, p53 and TdT. EAC: Ehrlich ascites carcinoma;
DADS: diallyl disulfi de; TdT: terminal deoxynucleotidyl transferase cells seemed apoptotic, after treatment with DADS, as they
were shrunk and had blebbing plasma membrane, apoptotic
DISCUSSION bodies and fragmenting nuclei which are considered as
[28]
phenotypical or morphological signs of apoptosis. In
The goal of cancer chemoprevention is to slow, to block addition to these histological results, immunohistochemical
or to reverse the process of carcinogenesis. With regard to results depicted that the expression of Bcl-2 working
this principle, the study is a trial to evaluate the anti-tumor primarily by blocking apoptotic pathway, was noticeably
[29]
72 Hepatoma Research | Volume 1 | Issue 2 | July 15, 2015