Assalamualaikum

Good morning everyone. The honour, dr. tonang, dr. ratih, dr.setyo. And to all my
beloved friends.

My name is Darma Aulia Hanafi, from Pendidikan Dokter.

First of all, before I start. I would like to say thank you for all. Because, being here, is a
beautiful experience of my life and being here is also my unexpected story.

Okay, lets start. in this good chance, let me present to you about my paper. The tittle is
“Potential Combination Of Curcumin And Epigallocatechin-3-Gallate As The
Chemopreventive Therapy Of Breast Cancer”.

As we know, cancer is the leading cause of death in both the developed and developing
countries. One common malignancy is breast cancer. Now, let we talk about breast
cancer.

Here, I present to you, some facts about the disesase.

First, somebody said that, breast cancer is the most common form of cancer among the
woman. And being woman is the main risk for breast cancer. Why? Lets look the second
fact. The second says that, a man also can get the disease. But, breast cancer is about
100 times more common among women then men.

The third, the fact says, 1 in 8 woman, will develop breasc cancer in her lifetime.

And, unfortunately, every 13 minutes, somenone dies from breast cancer.

Next, and 8 out of 9 women with breast cancer, have no family history of the disease.

The six fact says that, breast cancer risk increase with age.

Over all, it says that, breast cancer is the 2nd leading causes of cancer death in woman.

Now, lets look what WHO said…

WHO said that, in 2004 : more than 1,2 million woman in this world diagnosed by breast
cancer. And 8 years after that, is about, 1,6 million woman cases of breast cancer and
14,7% death cases in this world happens because breast cancer.

What about in out country?

It looks there is no many different. In the year 2012,
about 133,52 cases of breast cancer per 100.000 people
estimated of the total cases : 299.673 (16,4%) 1

So, it is important to know breast cancer as a danger disease in our country, even in this
world.

Nowadays, the therapy for this disease, is include surgery, chemotherapy or

radiotherapy. But is says, the therapy is not satisfying.

For example, the anticancer drugs, as the usually therapy used in hospital. Anticancer
drugs woks for the cancer, but unfortunately it is non selective. It means, it can destroy
not only the cancer cell but the normal cell too. Because of that, the use of anticancer
drugs, will cause various side effects. The use of large doses of cytostatic drugs also pose a
problem as more and more abnormal cells are infected and die. In addition, the high cost of
treatment is also a significant obstacle. . Belum lagi kemungkinan kejadian resisten obat dapat
terjadi

• Dg metode pengobatn pd saat ini, 1/3 jml pasien tertolong melalui pembedahan
dan terapi radiasi.

• Kesembuhan hampir seluruhnya terjadi pd pasien yg penyakitnya belum

menyebar pd saat pembedahan.

• Setelah terjadi metastasis dibutuhkan pendekatan sistemik melalui kemoterapi

kanker, di samping pembedahan, radiasi dan kemoterapi ajuvan. Pd keadaan ini,
pengobatan tdk m’nyembuhkn tetapi hanya bersifat paliatif thd gejala,
p’ncegahan komplikasi, support psikologik dan perpanjangan hidup yg berarti.

Prevention and treatment efforts continues to be made. The new study present that
chemopreventive is a new strategy can be used.

Pemahaman tentang proses karsinogenesis merupakan pengembangan strategi dalam

pengobatan penyakit kanker. Pendekatan terapi kanker menggunakan agen kemopreventif
 lebih menjanjikan daripada obat antikanker konvensional. Agen kemopreventif sendiri
didefinisikan sebagai senyawa yang menghambat dan menekan proses

karsinogenesis pada manusia sehingga pertumbuhan kanker dapat

dicegah (Kakizoe, 2003).

Agen kemopreventif mempunyai target spesifik melalui mekanisme-mekanisme

molekuler. Ketidaknormalan pada daur sel dan regulasi apoptosis, peningkatan enzim
COX-2 dan proses angiogenesis hanya terjadi pada sel yang terkena kanker. Oleh karena itu,
agen kemopreventif relatif aman dan tidak berpengaruh pada sel normal
(Chang dan Kinghorn, 2001).

Curcumin and epigallocatechin-3-gallate (EGCG) has potential as a chemopreventive agent, so

that the utilization can be a new strategy in the treatment of breast cancer. Both have proven their
use in vitro and in vivo.

So, in this paper, the problem to solve is How does the potential combination of
curcumin and epigallocatechin-3-gallate as a chemopreventive therapy of breast
cancer?

The purpose…

The benefit…

The material and methods we use is by literature review. The collection of data and
information obtained through the new and relevant of scientific journals and presentation of
research results to experts. The data were obtained using a trusted search engine such as Proquest
(http://search.proquest.com/), PubMed (http://ncbi.nlm.nih.gov/pubmed) and Google Scholar
(http://scholar.google.com ) to enter a number of keywords, such as curcumin, epigallocatechin-
3-gallate, chemopreventive and breast cancer. Inclusion criteria used are articles, journals,
books, and research or exposure to experts, while the exclusion criteria are opinion article that
without including the name of the author.

 Curcumin, a natural component of the rhizome of curcuma has emerged as one of the
most powerful chemopreventive and anticancer agents.
 Studi eksperimental telah berhasil membuktikan bahwa pengonsumsian curcumin
dapat mengurangi kejadian kanker (Tiffany, 2008). Ada bukti substansial dalam model
praklinis bahwa curcumin merupakan agen kemopreventif diet ampuh (Bachmeier et al..
2008, Chuang et al.. 2000, Huang,. 1997).
Sifat antikarsinogenik dan kemopreventif curcumin terbukti efektif in vitro pada
berbagai sel kanker payudara melalui interaksinya dengan molekul-molekul yang
berhubungan terhadap siklus hidup sel seperti apoptosis, proliferasi, invasi dan metastasis
dari sel kanker payudara (Salim et al., 2014).
Bagaimana mekanisme curcumin bekerja dalam terapi kanker payudara telah
dibuktikan melalui berbagai penelitian. Penelitian Shao et al. membuktikan bahwa curcumin
memiliki berbagai efek supresif yang berbeda terhadap sel kanker payudara in vitro (ER-
positive dan ER-negative).
Efek supresif yang pertama, yaitu sebagai antiproliferatif. Curcumin dapat
menghambat proliferasi sel kanker payudara, baik pada sel kanker ER positive (MCF-7)
maupun sel kanker ER negative (MDA-MB-231). Selain itu, dosis tinggi curcumin dapat
memblok alur ekspresi gen ER (esterogen-related) seperti ekspresi gen PS2 dan TGF-α.
Sehingga, diduga efek antiproliferatif curcumin adalah melalui penghambatan jalur ekspresi
gen ER (Shao et al., 2001). Penelitian lain mengatakan bahwa sifat antiproliferatif curcumin
juga melalui perusakan struktur benang spindel sehingga tidak terjadi pembelahan
kromosom (Holy, 2002).
Shao juga membuktikan bahwa curcumin memiliki efek antiinvasif pada sel kanker
payudara ER-negative MDA-MB-231. Efek antiinvasif dari curcumin adalah melalui
penurunan regulasi MMP-2 dan peningkatan regulasi dari TIMP-2. MMP-2 dan TIMP-2
adalah molekul efektor yang berfungsi dalam pengaturan invasi sel tumor (Nakahara et al.,
1997).
Efek supresif lainnya dibuktikan dengan penurunan tingkat transkripsi VEGF dan b-
FGF pada ER-negative MDA-MB-231. VEGF dan b-FGF merupakan faktor angiogenesis
 sel tumor. Kedua molekul tersebut dibutuhkan sel tumor untuk berkembang. Sehingga,
diketahui apabila curcumin juga berperan sebagai antiangiogenesis.
Penelitian lain menyebutkan bahwa curcumin dapat menginduksi apoptosis pada sel
kanker payudara dengan meningkatkan ekspresi gen p21, rasio perubahan BAX menjadi
BCL2 serta modulasi gen BRCA1 (Chiu dan Cheng, 2009).
Menariknya lagi, curcumin dapat menginduksi degradasi HER2/ NEU (onkogen yang
sering bermutasi pada kanker payudara dan menyebabkan prognosis buruk) (Cho et al.,
2007).

EGCG berperan sebagai agen kemopreventif melalui sifatnya yang dapat

menyebabkan apoptosis dan menghentikan siklus sel yang telah mengalami kerusakan DNA
atau sel kanker (Naghma et al., 2006).
Apoptosis diinduksi melalui kondensasi kromatin nukleus, aktivasi enzim caspase-3
(suatuprotease yang dapat memecah protein hingga menyebabkan fragmentasi DNA), dan
depolarisasi membran mitokondria sehingga dapat melepaskan sitokrom c ke sitosol.
Sitokrom c akan membentuk ikatan dengan protein sitosol yang dapat menyebabkan aktivasi
enzim caspase (Robbin, 2003).
Peran lain dari EGCG adalah mencegah cell signaling untuk hiperproliferasi sel.
Pencegahan tersebut dapat melalui jalur yang berbeda, seperti jalur nuclear factor-kb, jalur
MAPKs dan aktifasi protein-1, jalur EGFR, dll. Selain melalui pencegahan cell signaling,
EGCG dapat mencegah hiperproliferasi sel dengan menghentikan proses pembelahan sel
melalui penghambatan sintesis enzyme cyclin-dependent kinase sehingga proses G1 sel akan
terganggu. Selain itu, EGCG juga akan mengaktifkan p21 dan p27 dan mengurangi sintesis
siklin D. Protein 21 akan membentuk ikatan dengan CDK 2 sehingga CDK 2 tidak dapat
berikatan dengan siklin E pada fase G1. Hal ini akan menyebabkan sel gagal memasuki fase
S dan otomatis gagal mencapai fase mitosis atau pembelahan (Naghma, 2006).

Form all of the explanation before, we can conclude that Curcumin and EGCG have
potential as therapeutic breast cancer because it has the ability to act as a
chemopreventive agent. So, the combnation hopefully will increase the effectivity and
efficiency of breast cancer therapy.

But, we also know, that Further research is needed to study the suitable form in the
combination of curcumin and EGCG as a chemopreventive therapy of breast cancer.
Besides that, the side effects and how big the concentration of substances used in
therapy is also worth to know.