Bcl2 Gene Expression Profile on Administration of Novel

Active Compound from Soursop Leaves (SF-1603) as a New

Molecular Target in Liver Cancer Therapy

Maya Tejasari

, Siti Aminah Abdurachman

, Dwi Prasetyo

, Herri S. Sastramihardja

1.Histology Department, Faculty of Medicine, Bandung Islamic University, Indonesia

2.Professor of Clinical Farmacology, Faculty of Medicine, Bandung Islamic University, Indonesia

3.Professor of Internal Medicine Department, Faculty of Medicine, Padjadjaran University,Indonesia

4.Professor of Pediatric Department, Faculty of Medicine, Padjadjaran University, Indonesia

Keywords: Apoptosis, Bcl-2, Liver Cancer, Soursop (Annona Muricata), Targetted Therapy

Abstract: Most cases of liver cancer present in advanced stages so the prognosis remains poor. Apoptotic

dysregulation of liver cancer cells by BCL-2 gene expression is linked to tumor progression and resistance

to treatment. Soursop plant compound is believed will be able to induce apoptosis by interfering Bcl2 gene

expression. The objectives of the study was to explore the role of novel active compound isolated from

soursop leaves againts Bcl2 gene expression in order to find new molecular target for liver cancer therapy.

This study was in vitro experimental to assess active compound (SF-1603) effects on Bcl2 mRNA

expression. Treatment groups were treated with SF-1603 dosage of 0,5xIC

, IC

and 2xIC

. Observations

were assessed in hours 0, 24, 48, and 72. The results showed that Bcl-2 gene optimum expressions were

achieved with 2xIC

dose at hour 24. There were strong correlation between Bcl-2 gene expression with

apoptosis level (r=0,558). This evidence indicates that administration of SF-1603 promote expression of

Bcl-2 gene to produce a peak signal that activate the apoptosis. It was concluded that SF-1603 affect Bcl2

gene expression as liver cancer therapy molecular target on HepG2 cell line culture.

1 INTRODUCTION

As an effort to reduce mortality, various studies to

find effective treatments for liver cancer are still

being developed. Curative approaches such as

surgery and transplantation can only be done on a

limited basis due to various causes such as lack of

donors and considering its effects on liver function.

Therapy recommendations based on the

classification of the Barcelona Clinic Liver Cancer

(BCLC) for liver cancer with advanced stages are a

systemic chemotherapy. Curative approaches such

as resection and transplantation can only be limited

to patients with early stage liver cancer.

Chemotherapy is still the best choice for patients

with advanced liver cancer, however until now the

effectiveness of chemotherapy in liver cancer

patients is often considered relatively ineffective.

This therapeutic option for patients with liver cancer

is still very limited which is also one of the reasons

for the prognosis of liver cancer remain poor. (Ho et

al., 2009, Huynh et al., 2010, Lencioni et al., 2008,

Robotin et al., 2009, Park et al., 2006, Ghassan and

Abou-alfa, 2004, Wirth et al., 2005, Sherman et al.,

Bruix and Sherman, 2005)

Systemic chemotherapy has been shown

repeatedly to provide no benefit in improving

survival, regardless of whether it is given as a single

agent or as a combination chemotherapy part.

Systemic chemotherapy using existing

chemotherapy agents is generally stated to be

relatively ineffective for liver cancer. Liver cancer is

conciders resistant to chemotherapy because of the

high mutation load and also the mechanism of drug

resistance. The mechanism of resistance that arises

relates to the administration of low-dose

chemotherapy because it considers liver dysfunction

and is also carried out to reduce toxicity (Park et al.,

2006, Wirth et al., 2005, Ghassan and Abou-alfa,

2004)

Although many chemotherapeutic agents have

been tested, the role of systemic chemotherapy for

liver cancer remains unclear. New therapeutic

Tejasari, M., Abdurachman, S., Prasetyo, D. and Sastramihardja, H.

Bcl2 Gene Expression Proﬁle on Administration of Novel Active Compound from Soursop Leaves (SF-1603) as a New Molecular Target in Liver Cancer Therapy.

DOI: 10.5220/0008790800570064

In Proceedings of the 2nd Syiah Kuala International Conference on Medicine and Health Sciences (SKIC-MHS 2018), pages 57-64

ISBN: 978-989-758-438-1

strategies with more specific targets are needed to

improve treatment effectiveness. (Ghassan and

Abou-alfa, 2004, Park et al., 2006) There are no

prospective controlled studies showing that systemic

chemotherapy prolongs the survival of liver cancer

patients compared with supportive care. (Park et al.,

2006, Ghassan and Abou-alfa, 2004, Wirth et al.,

2005)

Antihormonal therapy with tamoxifen or

octreotide does not provide better patient survival.

Therapeutic strategies based on molecular targets

through pathway intervention signal transmission

and apoptotic regulation, offering new hope for

more effective treatment options. Potential targets

for systemic chemotherapy strategies in liver cancer

include mechanisms of oxidative and inflammatory

stress, growth factors, cell cycle checkpoints,

oncogene viruses, telomere shortening,

carcinogenesis, stem cells, angiogenesis and

antiapoptosis. (Wirth et al. , 2005, Park et al., 2006,

Ghassan and Abou-alfa, 2004) Dysregulation of

apoptosis influence the process of carcinogenesis,

progression of the tumor and tumor resistance to

radio-chemotherapy, therefore the development of

anticancer agents by inducing apoptosis is very

potential to be developed. Understanding in genetics

and treatment has improve a lot, but liver cancer

remains a deadly disease causing high mortality.

Further studies are needed to identify agents that

have more effective activity against liver cancer.

Cancer occurs because of fundamental changes

in cell physiology, one of the common

characteristics of which is avoiding apoptosis,

therefore the target of developing cancer therapy

agents is directed to induction of apoptosi. (Cha and

DeMatteo, 2005, Ho et al., 2009) Neoplastic cell

accumulation can occur not only because of

activation of oncogenes that promote tumor growth

or inactivation of tumor suppressor genes that

suppress growth, but also because of dysregulation

in genes that control apoptosis. As cell growth is

controlled by growth and suppressor genes, cell

survival is also controlled by genes that promote and

inhibit apotosis (Kumar et al., 2003, Ho et al., 2009)

Apoptosis is a form of programmed cell death

that depends on the results of intracellular gene

expression. The apoptosis process is divided into

two phases, initiation phase and execution phase.

Apoptosis initiation occurs because of signals

transmission from different pathways, namely the

extrinsic pathway (death receptor pathway) and

intrinsic pathway (mitochondrial pathway). These

two pathways eventually activate the caspase

enzyme and relate to each other in several stages.

(Kumar et al., 2003, Xu et al., 2010, Liu et al., 2011)

Apoptosis is induced by a cascade of sequences

of molecular events initiated through many

pathways that eventually activate caspase enzymes

(Kumar et al., 2003, Wirth et al., 2005, Chiu et al.,

2003) Apoptosis processes can be divided for two

phases, namely (Kumar et al., 2003, Martin)

initiation phase, when the caspase enzyme is

catalyzed to become active and the execution phase,

when the caspase enzyme causes cell death.

Apoptosis initiation occurs because of signals from

different pathways, namely the extrinsic pathway

(death receptor pathway) and intrinsic pathway

(mitochondrial pathway). Both of these pathways

eventually activate caspase enzymes and relate to

each other in several stages. (Kumar et al., 2003)

Intrinsic pathway involves one of the pro and

antiapoptotic molecules including Bcl-2.

Intrinsic signaling pathways are initiated by

increased mitochondrial permeability and release of

proapoptotic molecules into the cytoplasm, without

the involvement of death receptors. Hormones,

growth factors and other survival signals stimulate

antiapoptotic production from the Bcl-2 protein

group. Two proteins which are the main

antiapoptosis moleculs are Bcl-2 and Bcl-x. Both of

these antiapoptotic proteins are normal in the

mitochondrial membrane and cytoplasm of the cell.

(Kumar et al., 2003, Ho et al., 2009, Xu et al., 2010,

Robotin et al.,2009) There is an increase in

expression of Bcl2 and IAP in liver cancer, which is

an antiapoptotic protein resulting in apoptosis

inhibition via intrinsic pathways. (Chang Y.,2011,

Bassiouny A et al.,2008, Yildiz L et al.,2008)

The principal of intrinsic pathway is the

existence of a balance between pro-apoptotic

molecules such as Bax, Bak, and Bim with

antiapoptotic molecules such as Bcl2 and Bcl-xl,

which control mitochondrial permeability and

release of factors that induce cell death in normal

mitochondria. Mitochondria play an important role

in this pathway by releasing cytochrome c, which

eventually forms a complex with apoptosis-inducing

factor 1 (APAF-1), procaspase- 9 and ATP. Inside

this complex, procaspase-9 is activated to caspase-9,

which then triggers caspase-3 as executor caspase.

(Kumar et al., 2003, Ho et al., 2009, Xu et al., 2010)

In our study, induction of cell apoptosis was

investigated through one of the intrinsic pathways

which would be proven biochemically with changes

in the Bcl2 expression.

Bcl-2 is a protein family that is a CED-9

homologue found in mammals. Bcl-2 was first

SKIC-MHS 2018 - The 2nd Syiah Kuala International Conference on Medicine and Health Sciences

discovered in B-cell lymphoma as a proto oncogen.

Bcl-2 gene overexpression is a protective

mechanism to deal with various stimuli that cause

cell death. Bcl-2 gene is responsible for synthesizing

protein bcl-2. The Bcl-2 protein family consists of

antiapoptosis groups, namely bcl-2, bcl-xl, bcl-w,

Mcl-1, Nr13, and A1 / Bfl1, as well as proapoptosis

groups namely Bax, Bak, Bok, Diva, Bcl-xs, Bik,

Bim, Hrk, Nip3, Nix, Bad, and Bid. These proteins

are characterized by the Bcl-2 homology (BH)

domain in their structures, namely BH1, BH2, BH3,

and BH4 (Lu et al., 2011, Cagle and Allen, 2009,

Marschitz et al., 2000)

The proapoptosis group has two subfamily,

multidomain groups (Bax, Bak, Bok, Diva, and Bcl-

xs) and groups that only have BH3 domains (Bik,

Bim, Hrk, Nip3, Nix). This relative ratio between

pro protein and antiapoptosis determines cell

sensitivity to various apoptotic stimuli. Proapoptosis

proteins that have been studied well are Bax and

Bid. Exposure to various apoptotic stimuli causes

translocation of Bax from the cytosol to the

mitochondrial membrane. Bax oligomeration in the

mitochondrial membrane together with other

proapoptotic proteins, Bak eventually releases

cytochrom-c from within the mitochondria to the

cytosol. Other proapoptotic proteins, especially

those that only have BH3 domains, play a role in the

Bax-Bak oligomeration process in the mitochondrial

membrane. Bcl-2 antiapoptotic protein plays a role

in inhibiting Bax-Bak oligomeration in the

mitochondrial membrane and eventually inhibits the

release of cytochromic cytosol (Marschitz et al.,

2000, Lu et al., 2011, Cagle and Allen, 2009)

Hepatocarcinogenesis is a slow process, genomic

changes that progressively alter hepatocellular

phenotypes and produce cellular intermediates that

develop into hepatocellular carcinoma (Thorgeirsson

and Grisham, 2002, Cha and DeMatteo, 2005) In

liver cancer pathogenesis, apoptotic dysregulation

occurs in the form of low Fas expression which

inhibits caspase-8 and caspase-3 activation which

ultimately inhibits the apoptosis process through the

extrinsic pathway, and an increase in Bcl2 and IAP

expression which inhibits cascapse 9 activation and

caspase 3 which ultimately inhibits the apoptosis

process through intrinsic pathways. (Kumar et al.,

2003, Ho et al., 2009, Xu et al., 2010, Bassiouny A

et al.,2008, Cagle and Allen, 2009,Yildiz L et

al.,2008) Based on this thought, a study was

conducted to observe Bcl2 gene profile as one of the

genes that play a role in the liver cancer

pathogenesis.

Natural polyphenols are a large group of

compounds derived from plants, which are

chemically characterized by two or more phenol

units (Dai and Mumper, 2010, Fraga and Oteiza,

2011) Some chemists know the term polyphenols as

White-Bate-Smith Swain-Haslam wihch is described

in several characteristics. (Quideau et al., 2011) This

definition does not include low molecular weight

structures, which have been shown to have potential

benefits for human health. There are thousand

compounds derived from plants with higher

biological potential, which only have one or more

aromatic rings and at least two hydroxyl groups,

categorized as polyphenols. (Sies, 2010)

Natural polyphenols are secondary metabolites

derived from plants that are produced as defense

agents against various types of stress, such as

ultraviolet radiation, pathogenic aggression, low soil

fertility, changes in ambient temperature and

drought. (Dai and Mumper, 2010, Manach et al.,

2004) Based on its chemical structure, there are four

main classes of polyphenols: phenolic acids,

flavonoids, stilbenes, and lignans (Manach et al.,

2004, Bravo, 1998) Knowledge and implications of

these compounds on human health including their

effects on cancer (Kampa et al., 2007, Guo et al.,

2009, Korkina et al., 2009) nervous system

protection, (Zhao, 2009, Gutierez-Merino et al.,

2011) cardiovascular system dysfunction and

damage, (Sies, 2010, Grassi et al., 2009) metabolic

syndrome, (Agouni et al., 2009, Cherniack, 2011)

diabetes, (Milne et al., 2007) aging, (Queen and

Tollefsbol, 2010, Accomando et al., 2010) and

various pathologies (Tejasari M et al., 2014) and

condotion related to inflammation. (Accomando et

al., 2010) Polyphenols have been used for thousands

of years as traditional medicine in eastern countries.

However, the inclusion of these compounds in

western medicine is still a pending issue, perhaps

because of lack information and still not widely

known scientifically. (Rodriguez et al., 2013,

Dashwood, 2007)

Annona muricata Linn is a plant generally

known as soursop or graviola which contain a large

group of phytochemicals that naturally have

anticancer activities with high selectivity between

cancer cells and normal cells. (Fraga and Oteiza,

2011, Song et al., 2014, Martin, 2006, Young et al.,

2005 , Sayers, 2011) There are much studies show

that the active ingredients of soursop leaves have

strong anticancer activity on various types of cancer

cell lines. (He et al., 2010, Xiao et al., 2011, Coloma

et al., 2002a). Other studies also report that active

from the leaves of scales proved to be able to induce

Bcl2 Gene Expression Proﬁle on Administration of Novel Active Compound from Soursop Leaves (SF-1603) as a New Molecular Target in

Liver Cancer Therapy

apoptosis, but research on the ability of soursop

leaves to induce apoptosis in liver cancer cells and

its mechanism of action has not been widely carried

out.(Coloma et al., 2002b)

This study aims to test the effect of

administration of pure compounds (SF-1603)

isolated from soursop leave, to analyze its ability to

induce apoptosis in liver cancer cells, and explore its

mechanism of action in inducing apoptosis by

analyze Bcl2 mRNA expression in liver cancer cell

line to determine potential pathways as a new

molecular target of liver cancer therapy.

2 MATERIAL AND METHODS

Materials used in this study was the pure compound

isolated from the soursop leaves code SF-1603,

HepG2 cell line (HB-8065TM) from the American

Type Culture Collection (ATCC), Dulbecco's

Modified Eagle Medium (DMEM ) containing 10%

fetal bovine serum (FBS), penicillin, streptomycin

and trypsin for cell culture.

2.1 HepG2 Cell Line Culture

HepG2 cell line used in this study were less than 15

passages. Cell were seeded into well in Medium

(DMEM / F12) containing 10% Fetal Bovine Serum,

previously release cells using trypsin 0.05% - EDTA

0,53mM, then added to the growth medium into a

cell suspension. The cells were counted using a

hemocytometer and planted with a cell density of

25,000 cells/mL and obseved at 0, 24, 48 and 72

hour at 37oC with 5% CO2 atmosphere. There were

control group and intervention group given SF-1603

with concentration of 0,5xIC50, IC50 and 2xIC50.

Determination of IC50 concentration was done using

3-4-5-dimetylthiazol-2yl-2,5-difenil tetrazolium

bromide (MTT) method.

2.2 Measurement of mRNA Expression

using Quantitative Real-time

Polymerase Chain Reaction

This study using real-time PCR for quantitative

analysis. The working principle of real time PCR is

similar to conventional RT-PCR with the

fundamental difference that is: (i) Analysis of

amplicons using fluorescent reporter and not using

conventional gel electrophoresis, (ii) amplicon can

be analyzed from each cycle, and not only when the

end point. This study uses SsoFast

EvaGreen

SUPERMIX containing a mixture of ready-made for

the qPCR reaction except the primer and template, ie

2x reaction buffer with dNTPs, sso7d-fusion

polymerase, MgCl2, EvaGreen dye and stabilizers.

2.3 Statistical Analysis

All quantitative data are representative of at least

three independent experiments. Values are expressed

as mean±SD. Statistical analyses were conducted

using independen test, ANOVA test and simple

linear regression. The statistical package IBM SPSS

Statistics 21 for Windows was used in the analysis.

2.4 Implications of Ethical Aspects

This study has obtained ethical approval from

Medical Research Ethics Committee Medical

Faculty Padjadjaran University No.988 /

UN6.C2.1.2 / KEPK / PN.

3 RESULTS AND DISCUSSION

The group with 0.5xIC

administration dose showed

the of Bcl2 mRNA expression in the treatment group

was much different from the control group. In

general, in the control group there were not many

changes, there was only a slight increase in the

expression from the 48th to 72nd hours, whereas in

the treatment group there were quite dynamic

changes. During the first 24 hours there was only a

slight decrease in Bcl2 mRNA expression in the

treatment group, whereas the control group did not

experience changes in expression level. From the

24th to the 42nd hours there was a sharp increase in

the expression level of reatment groups until it

reached the highest level, while the control group

only showed very little increase. From the 48th hour

to the 72nd hour there was a sharp decrease in the

level of expression in the treatment group to the

lowest point while the control group showed a slight

increase in expression.

In the group with the administration of IC

dose,

it was seen that the expression of Bcl2 mRNA in the

treatment group was significantly different from the

control group. There were not many changes in the

control group, there was only a slight increase in

expression from 48 hours to 72 hours, whereas in the

treatment group there was a quite dynamic change.

In the first 24 hours there was only a slight decrease

in Bcl2 mRNA expression in the treatment group

while the control group did not experience changes

in expression level. From the 24th to the 42nd hours

SKIC-MHS 2018 - The 2nd Syiah Kuala International Conference on Medicine and Health Sciences

there was a sharp increase in the expression level

until it reached the highest score, while the control

group only showed very little increase. From the

48th hour to the 72nd hour there was a sharp

decrease in the level of expression in the treatment

group to the lowest point while the control group

showed a slight increase in expression.

The group with the administration of 2xIC50

doses showed that overall the expression of Bcl2

mRNA in the treatment group was lower than the

expression of the control group. In the first 24 hours

there was a decrease in Bcl2 mRNA expression in

the treatment group, whereas in the control group

there was no change in expression level. From the

24th to the 72nd hours there was an increase in the

expression of Bcl2 mRNA in the treatment and

control groups, with the expression level of the

treatment group being around 3 times lower than the

control group. The lowest Bcl2 mRNA expression

occurred at the 24th hour and the highest was at 72

hours, both in the treatment and control groups.

The expression profile of Bcl2 mRNA in HepG2

cell line culture after administration of pure

compounds SF-1603 can be seen in Figure 1.

Figure 1: Bcl-2 expression profile based on observation

time in all groups, on HepG2 cell line culture after

administration of pure compound SF-1603.

The normality test was performed using the

Kolmogorov-Smirnov Test and the test results with

α = 5% showed that at 95% confidence level, all

data were normally distributed. (p> 0.05) To find out

the differences in of Bcl-2 mRNA expression after

administration of pure SF-1603 compound at each

dose and time of observation, we used dependent

test and analysis of variance (ANOVA) method by

making decisions using the F distribution table.

Based on statistical calculations using ANOVA

method with α = 5% obtained F count value

compared with Ftable value as shown in Table 1

which showed that the F

count

> F

table (0.05).

It can be

concluded that at 95% confidence level there were

significant differences in Bcl-2 expression between

each group in all doses and time of observation (p

<0.05).

Table 1: Test of different expressions of Bcl-2 in HepG2

cell Line culture between groups

Group mRNA Bcl-2 expression

F count F table:

(

0,05

)

Control group

0.5xIC

group

2xIC

roup

21.3872

8741

2.81647

ANOVA (Analisis of varians)

To determine the dose and time that produces the

optimum Bcl-2 mRNA expression for apoptosis

initiation, we used an average comparison test.

Figure 2&3 showed the administration of SF-1603

soursop leaf pure compound on HepG2 cell line

culture resulted in optimum Bcl-2 gene expression

for apoptosis initiation at a dose of 2xIC50 at 24

hours.

Figure 2: Effect of Doses on Bcl-2 Gene Expression on

All Observations time, After Giving Soursop Leaf Pure

Compounds to HepG2 Cell Line Culture.

Figure 3: Effect of Time Factors on Bcl-2 Genes in All

Doses, After Giving Soursop Leaves Compound to HepG2

Cell Line Culture.

Bcl2 Gene Expression Proﬁle on Administration of Novel Active Compound from Soursop Leaves (SF-1603) as a New Molecular Target in

Liver Cancer Therapy

Various chemical compositions have been

isolated from various parts of soursop plants such as

leaves, roots, bark, flesh and seeds. Some

phytochemicals have been reported to be isolated

and characterized from various parts of soursop

plants and one of them isolated from soursop leaves

has strong anticancer activity and is able to induce

apoptosis in liver cancer cells. (Tejasari et al., 2018)

Suppression of Bcl-2 gene expression will

initiate the process of apoptosis through intrinsic

pathways. This apoptotic pathway occurs due to

increased mitochondrial permeability and release of

proapoptotic molecules into the cytoplasm, without

the involvement of death receptors. Several growth

factors and other survival signals stimulate

antiapoptosis production from the Bcl-2 protein

group (Martin, Wirth et al., 2005, Kumar et al.,

2003, Albert and Johnson, 2002)

Lots of proteins that belong to this group which

all play a role in regulating the apoptosis process.

One of the proteins which is the main antiapoptosis

is Bcl-2 protein. This antiapoptotic protein is present

in the mitochondrial membrane and cytoplasm of

cells. When the cell receives a survival signal or

experiences stress, Bcl-2 will disappear from the

mitochondrial membrane and be replaced by

proapoptotic proteins such as Bak, Bax, and Bim

(Kumar et al., 2003, Albert and Johnson, 2002).

When Bcl-2 and / or Bcl-x level decreases,

permeability of the mitochondrial membrane will

increase so that some proteins are released which

can activate the caspase cascade. One of these

proteins is cytochrome c, which is known to play a

role in mitochondrial respiration. In cytosol,

cytochrome c binds to a protein called Apaf-1

(apoptosis activating factor-1, homologous with

Ced-4), and this complex activates caspase-9. Bcl-2

and Bcl-x may also directly inhibit Apaf-1 activation

so that in the absence of Bcl-2 and Bcl-x, Apaf-1

activation can occur (Albert and Johnson, 2002,

Kumar et al., 2003). is the caspase cascade initiation

process. It can be concluded that the essence of this

intrinsic pathway is the balance between pro-

apoptotic molecules and protective molecules that

control mitochondrial permeability and the release

of factors that induce cell death that are normally in

mitochondria. (Kumar et al., 2003).

The study conducted in 2005was reported that in

liver cancer pthogenesis, there was an increase in the

Bcl2 expression which is an antiapoptotic protein

and strengthened by a study in 2008 which stated

that Bcl2 activation played a role in the progression

towards liver cancer. (Bassiouny et al., 2008,

Coloma et al., 2002, Chang and Xu, 2000, Yildiz et

al., 2008, Wu et al., 1995, Liu and 2009, 2009)

Inhibition of apoptosis through the intrinsic

pathway involving the Bcl-2 gene is one of the

pathways involved in the pathogenesis of liver

cancer. The ability of SF1603 soursop leaf pure

compound to suppress the expression of Bcl-2 can

be seen in figure 1 which showed the expression

level of Bcl-2 was lower than the control group in all

treatment groups. This is reinforced by the graph in

figure 2&3 which showed the optimum point of

expression of Bcl-2 by calculating the dose and time

factors. Statistical test with ANOVA in Table 1

strengthens the evidence with conclusions on 95%

confidence levels there are significant differences in

Bcl-2 expression between each group in all doses

and time of observation (p <0.05), in HepG2 cell

line culture after the administration of soursop leave

pure compounds SF-1603.

To measure the correlation strength of Bcl2

expression with apoptosis level, a simple correlation

test was calculated using the Pearson formula, and

presence coeficcient correlation between Bcl2

mRNA expression and the level of apoptosis is

r=0,558, which means the strength of the correlation

is strong. With the ability of SF-1603 soursop leave

pure compound in suppressing the expression of

Bcl-2, this compound can be used as a candidate for

HCC therapy agent by making the Bcl-2 gene as a

molecular target of therapy to initiate the HCC

apoptosis induction process.

4 CONCLUSIONS

The study conclude that the novel soursop leaves

active compound (SF-1603) is a powerful anticancer

that affect Bcl2 gene expression in apoptosis

induction on liver cancer cell, so it can be used as a

candidate for new therapeutic agent for liver cancer

treatment with Bcl2 as a new molecular target

ACKNOWLEDGEMENTS

This research was made possible thanks to the full

support of the Faculty of Medicine, Bandung Islamic

University and Faculty of Medicine Padjadjaran

University, as well as with the cooperation of the

Chemistry Research Laboratory Graduate School of

Science, Padjadjaran University and Biotechnology

Laboratory Rajawali Hospital Bandung..

SKIC-MHS 2018 - The 2nd Syiah Kuala International Conference on Medicine and Health Sciences

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