SKRIPSI

TUTUT CHYNTIA RIZCA

UJI SITOTOKSISITAS FRAKSI ETANOL AKAR

Jatropha gossypifolia L. TERHADAP SEL

KANKER PAYUDARA MCF-7 DENGAN

METODE MTT ASSAY

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2017

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KATA PENGANTAR

Assalamu’alaikum warahmatullahi wabarakatuh

Alhamdulillahirobbil’alamin, atas segala nikmat iman, islam, kesempatan, serta

kekuatan yang telah diberikan Allah Subhanahuwata’ala sehingga penulis dapat

menyelesaikan skripsiyang berjudul “UJI SITOTOKSISITAS FRAKSI

ETANOL AKAR Jatropha gossypifolia L. TERHADAP SEL KANKER

PAYUDARA MCF-7 DENGAN METODE MTT ASSAY”. Shalawat beriring

salam untuk tuntunan dan suri tauladan Rasulullah Shallallahu’alaihiwasallam

beserta keluarga dan sahabat beliau yang senantiasa menjunjung tinggi nilai-nilai

islam yang sampai saat ini dapat dinikmati oleh seluruh manusia di penjuru dunia.

Skripsi ini disusun untuk memenuhi salah satu syarat untuk mencapai gelar

sarjana Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas

Muhammadiyah Malang. Selama kegiatan penulisan skripsi, penulis tidak luput

dari kendala yang dihadapi. Akan tetapi, kendala-kendala tersebut dapat diatasi

penulis berkat adanya bantuan, bimbingan dari berbagai pihak. Oleh karena itu

penulis ingin menyampaikan rasa terima kasih dan penghargaan yang sebesar-

besarnya kepada:

1. Siti Rofida, S.Si., M.Farm., Apt selaku dosen pembimbing I dan Ahmad

Shobrun Jamil, S.Si., MP. selaku dosen pembimbing II atas saran,

bimbingan, arahan serta saran dan motivasi kepada penulis sampai

terselesaikannya skripsi ini.

2. Engrid Juni Astuti,S.Farm., M.Farm., Apt selaku dosen penguji I dan

Andri Tilaqza, S.Farm., M.Farm., Apt. selaku selaku dosen penguji II yang

telah banyak memberikan saran dan masukan demi kesempurnaan skripsi

ini.

3. Yoyok Bekti Prasetyo, S.Kep, M.Kep., Sp.Kom selaku Dekan Fakultas

Ilmu Kesehatan Universitas Muhammadiyah Malang.

4. Nailis Syifa, S.Farm., M.Sc., Apt., selaku Ketua Program Studi Farmasi

Universitas Muhammadiyah Malang.

5. Ika Ratna Handayanti S.Farm., M.Sc., Apt selaku dosen wali yang telah

memberikan saran, nasehat, motivasi, dan bimbingannya selama ini.

6. Laboratorium Parasitologi Fakultas Kedokteran Universitas Gajah Mada

khususnya Rumbiwati, ST., M.Sc. dan Prof. dr. Supargiyono, DTM&H.,

v

SU., Ph.D., SpParK. yang membantu dan mengarahkan selama proses

penelitian.

7. Sovia Aprina Basuki S.Farm., M.Si., Apt. selaku Kepala Laboratorium

Farmasi yang telah memberikan fasilitas selama melakukan penelitian.

8. Keluargaku tercinta Ayah, Ibu, dan Adik, yang tidak pernah lelah

memberikan motivasi, nasehat, dan kasih sayangnya tiada henti yang telah

mendo’akan dan mendampingi sampai dengan selesai mengerjakan

skripsi.

9. Dosen-dosen Farmasi Universitas Muhammadiyah Malang dengan

dedikasinya dalam dunia pendidikan atas ilmu selama menempuh kuliah.

10. Untuk semua anggota tata usaha program studi farmasi fakultas ilmu

kesehatan universitas muhammadiyah malang, yang telah banyak

membantu untuk kebutuhan administrasi kelengkapan skripsi.

11. Teman terbaikku (Deviana, Yeni, Parista, teman-teman Farmasi C),

Teman penelitian seperjuangan (Wulan, Linda, Fika, Irul, Nikma, Risa,

Tria, dan Fatma) yang selalu memberikan motivasi, bantuan, serta nasehat.

Terimakasih sudah menemani selama ini, kebersamaan ini tidak akan

pernah terlupakan.

12. Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf

dan terima kasih yang sebesar-besarnya. Semua keberhasilan ini tak luput

dari bantuan dan doa yang telah kalian semua berikan.

Tentunya skripsi ini masih jauh dari kesempurnaan. Karena pada dasarnya Penulis

adalah manusia biasa yang memiliki keterbatasan serta kemampuan yang berbeda-beda.

Oleh karena itu, penulis sangat berharap akan adanya masukan berupa saran dan kritik

yang sifatnya membangun untuk perbaikan di masa mendatang, Semoga Allah senantiasa

melimpahkan karunia-Nya dan semoga skripsi ini bermanfaat bagi masyarakat. Aamiin.

Wassalamu’alaikum warohmatullohi wabarokatuh

Malang, 20 Juni 2017

Penyusun,

Tutut Chyntia Rizca

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DAFTAR ISI

Halaman

LEMBAR PENGESAHAN .................................................................................. ii

LEMBAR PENGUJIAN ...................................................................................... iii

KATA PENGANTAR .......................................................................................... iv

RINGKASAN ....................................................................................................... vi

ABSTRAK .......................................................................................................... viii

ABSTRACT .......................................................................................................... ix

DAFTAR ISI .......................................................................................................... x

DAFTAR TABEL .............................................................................................. xiv

DAFTAR GAMBAR ........................................................................................... xv

DAFTAR LAMPIRAN ...................................................................................... xvi

DAFTAR SINGKATAN ................................................................................... xvii

BAB I PENDAHULUAN ...................................................................................... 1

1.1 Latar Belakang .................................................................................................. 1

1.2 Rumusan Masalah ............................................................................................. 4

1.3 Tujuan ............................................................................................................... 4

1.4 Manfaat Penelitian ........................................................................................... 4

1.4.1 Segi Akademik ........................................................................................ 4

1.4.2 Segi Masyarakat ...................................................................................... 4

BAB II TINJAUAN PUSTAKA ........................................................................... 6

2.1 Tinjauan Tanaman ............................................................................................. 6

2.1.1 Klasifikasi Tanaman ............................................................................... 6

2.1.2 Sinonim ................................................................................................... 6

2.1.3 Morfologi Tanaman ................................................................................ 7

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2.1.4 Daerah Asal dan Penyebaran .................................................................. 7

2.1.5 Manfaat dan Aktivitas Farmakologis ...................................................... 8

2.1.6 Kandungan Senyawa Kimia .................................................................... 8

2.2 Tinjauan Tentang Kanker .................................................................................. 9

2.2.1 Definisi .................................................................................................... 9

2.2.2 Siklus Sel .............................................................................................. 10

2.2.3 Proses Karsinogenesis ........................................................................... 11

2.3 Tinjauan Tentang Kanker Payudara ................................................................ 12

2.3.1 Definisi .................................................................................................. 13

2.3.2 Stadium ................................................................................................. 13

2.3.3 Penyebab dan Faktor Resiko ................................................................. 19

2.3.4 Gejala Kanker Payudara........................................................................ 21

2.4 Tinjauan Tentang Antikanker ......................................................................... 22

2.4.1 Tinjauan Tentang Doxorubicin ............................................................. 24

2.4.2 Tinjauan Senyawa Metabolit Sekunder Sebagai Antikanker ................ 25

2.5 Tinjauan Tentang Sel Vero ............................................................................. 27

2.7 Tinjauan Tentang Sel Kanker Payudara .......................................................... 28

2.8 Tinjauan Tentang Metode Ekstraksi ............................................................... 29

2.9 Tinjauan Tentang Fraksinasi ........................................................................... 32

2.10 Tinjauan Tentang Metode MTT (Microculture Tetrazolium Salt) Assay ..... 32

BAB III KERANGKA KONSEPTUAL ............................................................ 34

BAB IV METODE PENELITIAN .................................................................... 37

4.1 Lokasi Penelitian ............................................................................................ 37

4.2 Bahan dan Alat Penelitian ............................................................................... 37

4.2.1 Bahan Uji .............................................................................................. 37

4.2.2 Bahan Penelitian ................................................................................... 37

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4.2.3 Alat-Alat Penelitian .............................................................................. 38

4.3 Variabel Penelitian .......................................................................................... 38

4.3.1 Variable Bebas ...................................................................................... 38

4.3.2 Variable Tergantung ............................................................................. 39

4.4 Metode Penelitian............................................................................................ 39

4.4.1 Rancangan Penelitian ............................................................................ 39

4.4.2 Kerangka Operasional ........................................................................... 40

4.5 Prosedure Kerja ............................................................................................... 41

4.5.1 Pembuatan Ekstrak Uji ......................................................................... 41

4.6 Pembuatan Media ............................................................................................ 41

4.7 Pembuatan Larutan Induk dan Larutan Uji ..................................................... 45

4.7.1 Pembuatan Larutan Induk ..................................................................... 45

4.7.2 Pembuatan Larutan Uji ......................................................................... 45

4.8 Pembuatan Larutan Induk dan Larutan Uji Kontrol Positif (Doxorubicin) .... 46

4.8.1 Pembuatan Larutan Uji ......................................................................... 46

4.9 Uji Sitotoksisitas dengan MTT ....................................................................... 46

4.10 Analisis Data ................................................................................................. 48

BAB V HASIL PENELITIAN ........................................................................... 50

5.1 Persiapan Sel MCF-7 ...................................................................................... 50

5.1.1 Hasil Perhitungan Sel MCF-7 ............................................................... 50

5.1.2 Kebutuhan Sel MCF-7 Yang Ditransfer Untuk Pengujian MTT .......... 50

5.1.3 Hasil Sitotoksisias dari Ekstrak Etanol Akar Jarak Merah (Jatropha

gossypifolia L.) Terhadap Sel Kanker Payudara MCF-7 dengan metode MTT

Assay .............................................................................................................. 51

5.2 Persiapan Sel MCF-7 Untuk Doxorubicin ...................................................... 51

5.2.1 Hasil Perhitungan Sel MCF-7 ............................................................... 51

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5.2.2 Kebutuhan Sel MCF-7 Yang Ditransfer Untuk Pengujian MTT .......... 52

5.2.3 Hasil Sitotoksisias dari Doxorubicin Terhadap Sel Kanker Payudara

MCF-7 dengan metode MTT Assay ............................................................... 52

5.3 Persiapan Sel Vero ......................................................................................... 52

5.3.1 Hasil Perhitungan Sel Vero ................................................................... 52

5.3.2 Kebutuhan Sel MCF-7 Yang Ditransfer Untuk Pengujian MTT .......... 53

5.3.3 Hasil Sitotoksisias dari Doxorubicin Terhadap Sel Kanker Payudara

MCF-7 dengan metode MTT Assay ............................................................... 53

BAB VI PEMBAHASAN .................................................................................... 67

BAB VII KESIMPULAN DAN SARAN ........................................................... 61

7.1 Kesimpulan .................................................................................................... 61

7.2 Saran .............................................................................................................. 61

DAFTAR PUSTAKA .......................................................................................... 62

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DAFTAR TABEL

Tabel Halaman

II.1 Isolasi Senyawa Akar J. gossypifolia L. (Silva et al., 2014) ............................ 9

II.2 Perbedaan sel kanker payudara MCF-7 dan T47D......................................... 29

II.3 Indeks polaritas pelarut (Sarker et al., 2006) .................................................. 30

IV.1Kelompok perlakuan kultur sel kanker payudara (sel MCF-7) dan sel vero

dalam setiap percobaan. ................................................................................. 39

V.1 Data hasil uji sitotoksisitas fraksi EJG, doxorubicin, dan sel vero terhadap sel

kanker payudara MCF-7 dengan metode MTT assay .................................... 54

V.2 Hasil nilai IC50 fraksi etanol akar (Jatropha gossipifolia L.) dan Doxorubicin

terhadap sel kanker payudara MCF-7 dan sel vero dengan analisis data....... 56

xv

DAFTAR GAMBAR

Gambar Halaman

2.1(A) Akar J. gossypifolia L. dan (B) Daun, bunga, serta buahJ. gossypifolia L.

(Singh et al., 2013) ........................................................................................... 6

2.2Anatomi payudara (Dipiro,2011) ..................................................................... 13

2.3Tahap 0 (ASCO, 2005). ................................................................................... 14

2.4(A)Tahap IA, (B) Tahap IB prognostic grup 1, dan (C) Tahap IB prognostic

grup 2 (ASCO, 2005). .................................................................................... 15

2.5(A) Tahap IIA prognostic grup 1, (B) Tahap IIA prognostic grup 2, dan (C)

Tahap IIA prognostic grup 3 (ASCO, 2005).................................................. 16

2.6(A) Tahap IIB prognostic grup 1, dan (B) Tahap IIB prognostic grup 2 (ASCO,

2005). ............................................................................................................. 16

2.7(A) Tahap IIIA prognostic grup 1, (B) Tahap IIIA prognostic grup 2, (C)

Tahap IIIA prognostic grup 3, (D) Tahap IIIA prognostic grup 4, dan (E)

Tahap IIIA prognostic grup 5 (ASCO, 2005) ................................................ 17

2.8(A) Tahap IIIB prognostic grup 1, (B) Tahap IIIB prognostic grup 2, dan (C)

Tahap IIIB prognostic grup 3 (ASCO, 2005) ................................................ 18

2.9Tahap IIIC (ASCO, 2005). ............................................................................... 18

2.10Tahap 4 (ASCO, 2005). ................................................................................. 19

2.11 Struktur kimia doxorubicin (Pubchem, 2016) ............................................... 24

2.12Sel Vero (ATCC, 2008) ................................................................................. 27

2.13Sel MCF-7 (Biolabss, 2011) .......................................................................... 28

3.1 Skema Kerangka Operasional ......................................................................... 34

4.2 Skema Kerangka Operasional ......................................................................... 40

4.3 Perhitungan sel(CCRC, 2014) ......................................................................... 44

5.1 Kurva hubungan antara konsentrasi fraksi EJG dan doxorubicin terhadap %

sel hidup MCF-7 dan sel vero. ....................................................................... 55

xvi

DAFTAR LAMPIRAN

Lampiran Halaman

1. Daftar Riwayat Hidup ....................................................................................... 68

2. Surat Pernyataan................................................................................................ 69

3. Surat Determinasi Tanaman .............................................................................. 70

4. Sertifikat Kultur Jaringan .................................................................................. 71

5. Data Hasil Pembacaan Elisa Reader ................................................................. 72

6. Kerangka fraksinasi bertingkat n-Heksan, Etil Asetat, dan Etanol pada akar

Jatropha gossypifolia L. ................................................................................... 73

7. Hasil Screening Fitokimia Fraksi Etanol Akar J. gossypifolia L. dengan KLT

(Kromatografi Lapis Tipis) (Septiarini, 2016) ................................................. 74

8. Gambar Sitotoksik Dari Fraksi Etanol EJG Terhadap Sel Kanker Payudara

MCF-7 Dengan Metode MTT Assay ................................................................ 76

9. Gambar Sitotoksik Dari Fraksi Etanol EJG Terhadap Sel Vero Dengan Metode

MTT Assay ....................................................................................................... 77

10. Gambar Sitotoksik Dari Doxorubicin Terhadap Sel Kanker Payudara MCF-7

Dengan Metode MTT Assay ............................................................................. 78

11. Analisis Probit Fraksi Etanol EJG Untuk Sel MCF-7 ..................................... 79

12. Analisis Probit Fraksi Etanol EJG Untuk Sel Vero ........................................ 81

13. Analisis Probit Kontrol Positif Doxorubicin ................................................... 83

14. Perhitungan Data Elisa Reader Sel MCF-7 .................................................... 85

15. Perhitungan Data Elisa Reader Sel Vero ........................................................ 86

16. Perhitungan Data Elisa Reader Kontrol Positif Doxorubicin ......................... 87

17. Dokumentasi penelitian ................................................................................... 88

xvii

DAFTAR SINGKATAN

ACS = American Cancer Society

ATCC = American Type Culture Collection

BRCA = Breast Cancer Antigene

C = Celcius

cm = Centimeter

CCRC =Cancer Chemoprevention Research Center

DCIS = Ductal Carcinoma In Situ

Depkes RI = Departemen Kesehatan Republik indonesia

DES = Diethilstilbestrol

DMSO = Dimethyl Sulfoxide

DNA = Deoxyribose Nucleic Acid

EDTA = Ethylene Diamine Tetra Acid

EJG = Etanol Jatropha gossypifolia L.

FEJG = Fraksi Etanol Jatropha gossypifolia L.

ELISA = Enzyme-linked Immunosorbent Assay

FBS = Fetal Bovine Serum

FeCl3 = Besi (III) Klorida

G1 = Gap 1

G2 = Gap 2

HCl = Asam Klorida

HeLa = Henrietta Lacks

IC50 = Inhibitory Concentration 50

KLT = Kromatografi Lapis Tipis

KOH = Kalium Hidroksida

M = Mitosis

MCF-7 = Michigan Cancer Foundation-7

μg = Mikrogram

mg = Miligram

ml = Mililiter

mm = Milimeter

MK = Media Kultur

xviii

MTT = Microculture Tetrazolium Salt

NaOH = Natriom Hidroksida

NaHCO3 = Natrium Bikarbonat

NCI = National Cancer Institute

PBS = Phospat Buffer Salin

Riskesdas = Riset Kesehatan Dasar

S = Sintesis

SPSS = Statistic Program for Social Science

WHO = World Health Organization

62

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