Aktivitas Senyawa Trisindolina 5 Terhadap Ekspresi Gen c-Myc dan FoxO1, 3, 4 Pada Cancer Stem Cell

Fatoni, Muhammad (2022) Aktivitas Senyawa Trisindolina 5 Terhadap Ekspresi Gen c-Myc dan FoxO1, 3, 4 Pada Cancer Stem Cell. Masters thesis, Institut Teknologi Sepuluh Nopember.

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Abstract

Pengobatan terhadap proliferasi sel kanker payudara masih belum optimal karena terdapat cancer stem cell (CSC). CSC mampu melakukan self-renewal, inisiasi tumor dan metastasis. Overekspresi c-Myc pada kanker payudara membuat master faktor transkripsi onkogenik ini berpotensi sebagai target terapi kanker. Inhibisi c-Myc pada sel kanker dapat meningkatkan faktor transkripsi anggota family FoxO seperti FoxO1, 3, 4 serta target gen hilirnya yang terlibat dalam fase istirahat siklus sel, apoptosis dan autofagi. Trisindolina merupakan senyawa alami alkaloid timer indol yang toksik terhadap sel kanker. Penelitian ini bertujuan untuk mengetahui aktivitas senyawa trisindolina 5 pada CSC kanker payudara MDA-MB-231 melalui analisis sitotoksisitas, apoptosis serta ekspresi gen c-Myc dan FoxO1, 3, 4. Hasil uji sitotoksisitas MTT menunjukkan trisindolina 5 mampu menurunkan viabilitas CSC kanker payudara MDA-MB-231 dengan nilai IC50 13,127 µg/ml inkubasi 24 jam. Analisis flow cytometry menunjukkan trisindolina 5 mampu menginduksi apoptosis dengan persentase tertinggi pada konsentrasi 25 µg/ml sebesar 5,23%. Selanjutnya, analisis qPCR metode Livak mengindikasikan penurunan ekspresi c-Myc tertinggi terdapat pada trisindolina 5 konsentrasi 25 µg/ml sebesar 0,0746 kali lipat. Sementara peningkatan ekspresi FoxO1, 3, 4 tertinggi terdapat pada trisindolina 5 konsentrasi 25 µg/ml masing-masing sebesar 20,6452, 26,4709 dan 12,8341 kali lipat. Kesimpulan penelitian ini adalah trisindolina 5 konsentrasi 25 µg/ml mampu menurunkan tingkat ekspresi onkogen c-Myc serta meningkatkan ekspresi FoxO1, 3, 4, namun belum cukup efektif dalam mereduksi populasi CSC kanker payudara MDA-MB-231.
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The treatment of breast cancer cell proliferation is not optimal because there are cancer stem cells (CSCs). CSCs are capable to self-renewal, tumor initiation and metastasis. Overexpression of c-Myc in breast cancer makes this oncogenic master transcription factor a potential target cancer therapy. Inhibition of c-Myc in cancer cells can increase the transcription factors FoxO family members including FoxO1, 3, 4 and their downstream target genes involved in cell cycle arrest, apoptosis and autophagy. Trisindoline is an indole timer alkaloid natural compound which is toxic to cancer cells. This study aims to determine the activity of trisindoline 5 on CSCs breast cancer MDA-MB-231 through cytotoxicity, apoptosis and gene expression of c-Myc and FoxO1, 3, 4. The results of MTT assay showed trisindoline 5 able to decrease the viability of CSCs breast cancer MDA-MB-231 with IC50 13.127 µg/ml at 24 hours incubation. Flow cytometry analysis showed trisindoline 5 able to induce apoptosis with the highest percentage at a concentration of 25 µg/ml which is 5.23%. qPCR analysis indicated the highest decrease in c-Myc was found in trisindoline 5 concentration of 25 µg/ml with 0.0746-fold. Meanwhile, the highest increase FoxO1, 3, 4 expression was found in trisindoline 5 concentration of 25 µg/ml, 20.6452-fold, 26.4709-fold and 12.8341-fold respectively. The conclusion is trisindoline 5 concentration of 25 g/ml was able to reduce the expression of c-Myc and increase the expression of FoxO1, 3, 4, but it was not effective enough in reducing the population of CSCs breast cancer MDA-MB-231.

Item Type:	Thesis (Masters)
Uncontrolled Keywords:	Apoptosis, Cancer Stem Cell, c-Myc, FoxO, Trisindolina 5, Apoptosis, Cancer Stem Cell, c-Myc, FoxO, Trisindoline 5.
Subjects:	Q Science > QH Biology Q Science > QH Biology > QH301 Biology
Divisions:	Faculty of Science and Data Analytics (SCIENTICS) > Biology > 46101-(S2) Master Thesis
Depositing User:	Muhammad Fatoni
Date Deposited:	02 Feb 2023 04:34
Last Modified:	02 Feb 2023 04:34
URI:	http://repository.its.ac.id/id/eprint/95964

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