POTENSI SENYAWA PENTAGAMABORONON-0-FRUKTOSA (PGB-0- F) SEBAGAI AGEN KEMOTERAPI TERHADAP SEL KANKER PAYUDARA 4T1

YOGI ERTANTO, Prof. Dr. Edy Meiyanto, M.Si., Apt. ; Dr. Riris Istighfari Jenie, M.Si., Apt.

2018 | Tesis | MAGISTER BIOTEKNOLOGI

Senyawa analog kurkumin baru, Pentagamaboronon-0 (PGB-0) merupakan senyawa antikanker potensial serta dapat dikembangkan sebagai senyawa boron carrying pharmaceutical untuk pengobatan BNCT (boron neuron capture therapy). Namun senyawa tersebut memiliki kekurangan yakni kelarutan dalam air yang rendah. Tujuan penelitian ini adalah untuk mengeksplorasi aktivitas antiproliferatif dan anti-metastatik senyawa hasil kompleksasi PGB-0 dengan fruktosa, PGB-0-F terhadap sel kanker payudara 4T1. Uji sitotoksisitas dilakukan dengan metode MTT assay menunjukkan bahwa PGB-0-F memiliki nilai IC50 sebesar 33 µM pada perlakuan 24 jam sedangkan kombinasi senyawa PGB-0-F menghasilkan efek sinergis jika diberikan bersamaan dengan doxorubicin. Analisa siklus sel dengan PI-staining flow cytometry menunjukkan PGB-0-F memodulasi siklus sel yang menyebabkan S-phase arrest pada konsentrasi 34 µM dan 51 µM pada perlakuan 24 jam, yang didukung dengan adanya peubahan ekspresi protein cyclin A yang berperan penting pada fase S siklus sel. Selanjutnya, uji apoptosis PGB-0-F (34 dan 51 µM) menginduksi apoptosis sebesar 7,36 dan 7,18% dibandingkan kontrol sel tanpa perlakuan PGB-0-F. Uji produksi ROS intraseluler melalui perlakuan PGB-0-F 51 µM dengan DCFDA staining menghasilkan kenaikan ROS level sebesar 137% dibandingkan dengan kontrol sel. Adapun pengujian terhadap aktivitas anti-migrasi melalui metode scratch wound healing assay, menunjukkan PGB-0-F menghambat migrasi pada sel 4T1, sedangkan pada uji ekspresi MMP-9 dengan metode gelatin zymography menunjukkan adanya penurunan ekspresi protein tersebut. Berdasarkan uji anti-proliferatif dan uji anti-migrasi PGB-0-F berpotensi dikembangkan sebagai agen kemoterapi khususnya sebagai senyawa anti-migrasi. Kata Kunci : boron carrying pharmaceutical, PGB-0-F, Sel 4T1, proliferasi, migrasi

POTENCY OF PENTAGAMABORONON-0-FRUCTOSE (PGB-0-F) COMPOUND AS CHEMOTERAPY AGENT TOWARD 4T1 BREAST CANCER CELLS The new curcumin analogue compound, Pentagamaboronon-0 (PGB-0) is an potential anticancer compound which can be developed as boron carrying pharmaceutical for BNCT (boron neuron capture therapy) treatment. However, this compound has a limitation of low water solubility. The aim of this study was to explore the anti-proliferative and anti-metastatic activities of the PGB-0 complex with fructose (PGB-0-F) against 4T1 breast cancer cells. The cytotoxicity assay performed by the MTT assay method showed that PGB-0-F had an IC50 value of 33 µM during 24 hours treatment while the PGB-0-F combination gave a synergistic effect when administered simultaneously with doxorubicin. Analysis of cell cycle with PI staining flowcytometry showed that PGB-0-F modulated cell cycle with S-phase arrest at concentrations of 34 µM and 51 µM in 24 hour treatment, supported by expression change of cyclin A protein that plays an important role in the S phase cell cycle. Furthermore, PGB-0-F (34 and 51 µM) induced apoptosis by 7,36% and 7,18% compared to untreated cell. Intracellular ROS induction test through PGB-0-F treatment of 51 µM with DCFDA staining resulted an increase of ROS concentration of 1.4 times compared with cell control. The testing of anti-migration activity was performed by scratch wound healing assay method, showing PGB-0-F inhibited migration in 4T1 cells, whereas in MMP-9 expression experiment with gelatin zymography method showed a decrease of protein. Based on anti-proliferative tests and PGB-0-F anti-migration assays, PGB-0-F has a potency to be developed as chemotherapeutic agent especially as anti-migration agent. Keywords : boron carrying pharmaceutical, PGB-0-F, 4T1 Cells, proliferation, migration

Kata Kunci : boron carrying pharmaceutical, PGB-0-F, Sel 4T1, proliferasi, migrasi