ACTIVITY OF GEMCITABINE
BY EMODIN AGAINST
PANCREATIC
CANCER
Via Hayati1,
Endang Darmawan2
1Pharmacist
Program, Pharmacy
Graduate Program2, Faculty
of Pharmacy,
Ahmad Dahlan University,
Yogyakarta, Indonesia
Abstract
Objective
This
review article
aims to determine efektiftas
emodin when
combined with
gemcitabine for
pancreatic-cancer.
Methode
The presentation
all results
and discussion based
on a review journal
that carried
out from
various sources
journals: Pubmed,
NIH, IJO
(Journal of the
Institute of Oncology),
and google
scholar of
2003-2011. Then
carried out compiling
some journals
resulting in a
complete journal.
Results
Based on in vitro assays,
preclinical, and human data, emodin combination with gemcitabine may enhance
gemcitabine activity and reduced side effects as anticancer gemcitabine. Emodin
in vitro to inhibit the growth, suppress cell migration and invasion and
induces apoptosis SW 1990 cancer cells by inhibiting the growth of BxPC-3
cells. On the decline in preclinical testing regulation on Bcl / Bax and an
increase in the release of mitochondrial citokrom C leads to increased
apoptosis and decreased tumor volume and weight of the combination gemcitabine
+ emodin. While the human data, emodin used in conjunction with gemcitabine may
reduce the side effects of gemcitabine with a decline in the number of VEGF and
CA19-9 in the treated group (emodin + Gemcitabine) is significantly higher than
control group (gemcitabinea) P <0.05.
Conclusion
Use of
emodin which
together with gemcitabine
may enhance
the activity gemcitebine
and reduce side
effects. So it
can be recommended
as a treatment alternative
in the treatment of
pancreatic cancer.
Keyword : Pancreatic
cancer, emodin,
gemcitabine, combination.
1.
INTRODUCTION
Cancer is
one of the leading causes of death in
the United States,
caused by uncontrolled division of abnormal cells (BKEdwards et al, 2010). Pancreatic
cancer is the
fourth leading
cause of death,
PCAN (Pancreatic Cancer
Action Network) in
2011 in
the United Bunch
of approximately
44 030 people diagnosed
with pancreatic cancer
and 37
660 died of
the disease (PCAN, 2011). SEER (Surveillance Epidemiology
and Result) estimated 43 920
(22 090 men
and 21 830
women) diagnosed
with pancreatic cancer
and 37,390 will die
of pancreatic
cancer in 2012, this (Howlader N et al, 2012).
Pancreatic
cancer is known as the "silent disease" because in the early stages
of pancreatic cancer almost have symptoms. We must be wary of pancreatic cancer
because pancreatic cancer is a rare type of cancer but it is quite dangerous
and quite vicious, because pancreatic cancer can only be detected when it is
already at an advanced stage.
Treatment used
is ionizing
radiation, surgery and chemotherapy the
tumor tissue.
However, current methods
of cancer
pegobatan mnyebabkan severe systemic
side effects.
Gemcitabine is
the standard
drug treatment
of advanced pancreatic cancer, gemcitabine but have
side effects, toxicity
and drug resistance is large. For that
reason, much research
focuses on alternative
medicine based
padaekstrak plants. The
use of drugs
alternatives, especially when
used together
with conventional
medicine of anticancer
therapy. May
serve to reduce
side effects, increasing the
absorption of drugs
and strengthen
the immune
system konvensioanal body
to fight cancer
(MS Goldstein, 2003).
Emodin is an anthraquinone. In Pharmacology has
shown anticancer effects in several human
cancers. Liu
et al (2011) in
his study suggests
that emodin may
inhibit cancer
cell growth and induce apoptosis of
cancer cells.
Emodin has antipoliferatif and antimetastatik activity in
cancer cells both in vitro
and in vivo.
This study aims
to determine the
activity of gemcitabine after combined with emodin, expected by
the study could be used as
a reference for
anticancer therapy.
2.
METHODE
The presentation
all results
and discussion
based on literature study using PICO and journals from various sources: Pubmed, NIH, IJO (Journal of the Institute of
Oncology), and google scholar of 2003-2011. Then
do the compiling some
journals that
produces a
complete journal.
3.
RESULTS AND DISCUSSION
RESULTS
The results obtained
by searches made
5 journals including the
journal of research
in vitro, preclinical and
clinical trials.
Effect of emodin Data science
journal Gemcitabine
As Anticancer Activity Against shown in
Table 1.
No
|
Research
|
Methode
|
Actifity
|
Referensi
|
1
|
In vitro
|
- Tunel Assay,
- Imunohitochrmistry
- Western
bolt
|
Emodin
enhance the
antitumor
effects
of gemcitabine.
|
Chen H et al,
2011
|
Cell Kit-8 Assay and BxPC-3
Cell
|
Emodin
inhibits
the growth of
BxPC-3
cells
and work
synergistically
against
gemcitabine.
|
Zeng Yong et al,
2011
|
||
Emodin combined with gemcitabine
induced a higher percentage of growth inhibition and apoptosis in both
pancreatic cancer cell lines compared to gemcitabine alone.
|
Liu et al, 2011
|
|||
2.
|
Praklinik
|
Model xenograft
sel
|
Emodin and
gemcitabine
combination
resulted in increased
apoptosis
of cancer
cells.
|
Weitian et al,
2010
|
3.
|
Human Data
|
The use of a
combination of
emodin
and gemcitabine
in pancreatic
cancer
patients
can reduce
side effects.
|
Wang et al, 2011
|
Table 1. Effect
Of Emodin
On Activity
Of Gemcitabine Againts Pancreatic Cancer
DISCUSSION
Based on research that has been
done, emodin shown to increase the effectiveness of gemcitabine. Emodin in
vitro to inhibit the growth, suppress cell migration and invasion of SW 1990.
Test showed emodine western downregulated CD34, NF-kappaB, and MMP-9 in SW 1990
cells. 1990 SW Tues merupkan found in tumor cells (Liu et al, 2010). Chen et al
study (2010) showed that emodin can induce tumor cell apoptosis with a decrease
in Bcl-2/Bax regulation and increase the release of citokrom C (CytC).
Meanwhile, when combined with gemcitabine then emodin can enhance the antitumor
efficacy of gemcitabine as even at low doses, thereby reducing the toxicity effects
of gemcitabine. Zeng et al (2011) in his research revealed that emodin
significantly inhibited cell growth of BxPC-3, and work synergistically with
gemcitabine in inhibiting tumor cell proliferase BxPC-3. Synergism of action
can be achieved due to the induction of apoptosis in pancreatic cancer cells.
The experimental results showed that
emodin diindukis cells (40μmol / L) for 24, 48 and 72 hours had survival rates
79. 39%, 46. 35%, and 45. 44%, whereas the survival rate of BxPC-3 cells for 72
h at E & G is only 26. 62%, this indicates a significant difference between
gemecitabine induced cells alone (42.78%) and emodin alone (47.18%). Ratio of
early apoptotic cells BxPC-3 induced emodin (40μmol / L) for 24 hours and
gemecitabine (20 mol / L) was 4.70% + / - 1.54% and 11.20% + / - 1.41% , while
the ratio of early apoptosis of BxPC-3 cells induced E & G was 20.60% + /
-3.23%, the data showed significant differences from that induced by emodin or
gemecitabine alone (P <0.05).
Preclinical trials conducted Weitian
et al (2010), in athymic mice using xenograft models of SW 1990 cells are
injected IP (intraperitonial) with different groups, namely the N (sodium
chloride 0.9%), group E (40 mg emodin / kg), group G (gemcitabine 125 mg / kg)
and E + G (emodin 40 mg / kg and gemcitabine 80 mg / kg). The results obtained
after 1 week of injection was a significant decrease in tumor volume and the
average tumor weight of the average G + E combination group than the other
treatment groups. Tunel test showed the combination of E + G group had a
greater apoptosis than the other groups. Immunohistochemical analysis (IHC) and
Western blot (WB) shows cytochrome C in cytoplasm and Bax protein in the
combination E + G upregulated while Bcl decreased regulation as compared with other
groups, in other words there is a decrease in the regulation of Bcl / Bax and
an increase in the release citokrom C from the mitochondria that lead to
increased apoptosis.
Wang et al (2011) in
his research on the safety of
the combination of gemcitabine by emodin capsules of pancreatic cancer patients showed emodin capsules can reduce
the burden of
cancer patients. Data supporting these
studies, reductions in
VEGF and CA19-9 in
the treated group
(emodin + Gemcitabine) is significantly higher
than control
group (gemcitabinea) P
<0.05. Incidence
of bleeding
and gastrointestinal disorders due
to drug side
effects in
the treated group
was significantly lower than control kselompok. The
response rate in
cancer inhibition does
not occur
significant differences between
the treatment and
control groups.
4.
CONCLUSION
Based on the review journal that
has been done
can be concluded that emodin affects
the activity of
gemcitabine. Use
of emodin
in combination with gemcitabine may enhance
the activity of
gemcitabine in
the treatment of
pancreatic cancer, and
can reduce side effects
caused by gemcitabine.
5.
RECOMMENDED
Emodin and gemcitabine combination can
be used as a
therapeutic alternative for
the treatment of
pancreatic cancer.
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