Page 80 - Read Online

reduced while the pro-apoptotic and anti-tumor suppressor kidney of carbon tetrachloride-intoxicated rats. Different
protein p53 causing cell cycle arrest of EAC-cells, [30-32] was hypotheses have evolved to explain the mechanisms by
increased as a result of DADS treatment. The stimulating which DADS produced its anti-carcinogenic effects. García
effect of DADS on the expression of p53 may result from et al. reported that DADS exerted its anti-carcinogenic
[47]
inhibition of cyclin-dependent kinases. It was reported effect by inhibition of cytochromes CYP2E, CYP2A6 and
[33]
that p53 stimulation produced a dual effect on EAC-cells. CYP1A1 and activation of UDP-glucuronyl-transferase.
It may upregulate the pro-apoptotic protein Bax on one Knowles and Milner, Robert et al. and Oommen et al.
[37]
[35]
[36]
hand and/or mediate growth arrest involving p21 as a major stated that the anti-tumor effect of garlic may be due to
effector on the other. [28,34] Similar to the effect on p53, the the induction of apoptosis of tumor cells. Furthermore,
DNA fragmentation marker, TdT also increased as a result Iciek et al. attributed the anti-cancer effects of DADS to
[28]
[43]
of treatment with the tested compound. From these findings, both suppression of cell division (stimulation of cell cycle
it can be suggested that the induced inhibition of EAC-cell arrest) and induction of apoptosis in tumor cells. This latter
growth and proliferation by DADS are due to induction of postulation is concomitant with the present study, which
apoptosis and cell cycle arrest. These results and suggestion revealed a decreased expression of anti-apoptotic protein
are in accordance with other several publications. [35-37] Bcl-2 in cytoplasm and increased levels of pro-apoptotic
and cell cycle arrest protein in cytoplasm and nuclei as well
It was reported that in EAC-bearing mice, extensive formation as increased concentration of DNA fragmentation marker
of new capillary blood vessels (neovascularization or TdT in nuclei of tumors cells after treatment with DADS
angiogenesis) provides more nutrients and oxygen supply as compared with vehicle. This attribution was supported
to the highly divided EAC-cells leading to the induction of by imaging and semi-quantitative analysis which revealed
growth and proliferation. [38-40] Thus, it should not be excluded that the area in pixels, the percent area and the intensity
that DADS may have anti-angiogenic effects which in turn may of yellowish brown color of immunoreactive pro-apoptotic
have a crucial role in anti-proliferative effects. [15] protein, Bcl-2, decreased while those of the yellowish brown
colored immunoreactive apoptotic markers, p53 and TdT,
[41]
[14]
As suggested by Freitas et al. and Senger et al., the increased.
production of ascitic extracellular fluid in Ehrlich carcinoma
is said to occur due to increased capillary permeability In conclusion, DADS has effective anti-tumor potentials
present in the peritoneal cavity. This vascular change occurs against EAC-cells in both in vivo and in vitro studies. These
due to increased receptor expression for autocrine motility anti-tumor effects may be mediated via modulation of tumor
factor (AMF). AMF link to its receptor induces angiogenesis cell cycle as well as the balance between pro-apoptotic and
[14]
and changes in endothelial cell morphology causing a anti-apoptotic factors.
subsequent increase in vascular permeability with increased
[42]
amount of ascitic fluid in addition to the increasing number REFERENCES
of proliferated cells. In the present study, the volume of
EAC-aliquot relative to total cell count was increased as a 1. Bilecová-Rabajdová M, Birková A, Urban P, Gregová K,
result of DADS treatment. In our opinion, this means that Durovcová E, Mareková M. Naturally occurring substances and their role
the extra-cellular fluid volume was increased at the expense in chemo-protective effects. Cent Eur J Public Health 2013;21:213-9.
of EAC-cells which exhibited a greater rate of apoptosis 2. Jo HJ, Song JD, Kim KM, Cho YH, Kim KH, Park YC. Diallyl disulfi de
induces reversible G2/M phase arrest on a p53-independent mechanism
and death after treatment with DADS. This assumption was in human colon cancer HCT-116 cells. Oncol Rep 2008;19:275-80.
supported by the present histological results which depicted 3. Thakur VS, Deb G, Babcook MA, Gupta S. Plant phytochemicals
increased extracellular exudates in EAC-bearing mice treated as epigenetic modulators: role in cancer chemoprevention. AAPS J
with DADS. 2014;16:151-63.
4. Le Bon AM, Siess MH. Organosulfur compounds from Allium and the
chemoprevention of cancer. Drug Metabol Drug Interact 2000;17:51-79.
The present in vitro study indicated that DADS succeeded 5. Thomson M, Ali M. Garlic [Allium sativum]: a review of its potential
to produce amazing potential anti-tumor cytotoxicity and use as an anti-cancer agent. Curr Cancer Drug Targets 2003;3:67-81.
antiproliferative effects against EAC-cells. These results 6. Wen J, Zhang Y, Chen X, Shen L, Li GC, Xu M. Enhancement of diallyl
are in accordance with those obtained by many previous disulfi de-induced apoptosis by inhibitors of MAPKs in human HepG2
hepatoma cells. Biochem Pharmacol 2004;68:323-31.
authors who found that DADS cause marked inhibition of 7. Herman-Antosiewicz A, Singh SV. Signal transduction pathways
HepG2 cell proliferation [6,43,44] and HCT116 cell growth. [2,10] leading to cell cycle arrest and apoptosis induction in cancer cells
The present results are also in accordance with in vivo by Allium vegetable-derived organosulfur compounds: a review.
studies of Ahmed et al. [45] and Abdel-Aleem et al. [46] 8. Mutat Res 2004;555:121-31.
Belloir C, Singh V, Daurat C, Siess MH, Le Bon AM. Protective effects
who found that DADS had anti-tumor effects in liver and of garlic sulfur compounds against DNA damage induced by direct- and

Hepatoma Research | Volume 1 | Issue 2 | July 15, 2015 73