BIOACTIVITY OF Sargassum polycystum C. AGARDH EXTRACT AS ANTICANCER AND DNA METILTRANSFERASE (DNMT1) INHIBITOR

• Main Author: Widowaty, Windy
• Format: Dissertations
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/42140
• Institution: Institut Teknologi Bandung

Cancer is a desease involving abnormal cell growth that lead to cell death. Certain mutation involving specific genes can led to genetic instability. Epigenetic define as decrease in properties caused by gene expression without any change in DNA sequence. DNA methylation catalized by DNA Methyltransferase is the main mechanism of epigenetic. Several natural plants has been reported as DNMT1 inhibitor. Sargassum polycystum C. Agardh is type of brown seaweed (Phaeophyta) which is found in Indonesia, especially the beach of Sayang Heulang, West Java. Bioactivitivity of Sargassum polycystum C. Agardh extract from Indonesia, especially from the beach of Sayang Heulang as an antibacterial, antioxidant, anticancer and as an DNMT1 inhibitor has not been known. The aim of this research is to characterized bioactivity of Sargassum polycystum C. Agardh fractions as anticancer and as DNMT1 inhibitor selected based on their activity as antibacteria and antioxidant. The fractions that were successfully characterized were analyzed its component compounds using GC-MS. An extraction process using modified Folch method with chloroform : methanol : buffer pH 7.6 (2 : 1 : 0.8 v/v). The crude of each phase was tested as antibacterial, antioxidant and anticancer activity. The result showed that the aqueous-methanol extract has the potency as antioxidant with total percentage of free radical scavenging 80.25 ± 1.76 % while the crude chloroform extract as antibacterial agent with highest zone of inhibition 5.0 ± 1.0 mm (B. cereus) and Cytoxtocicity assay against breast cancer cell MCF-7 showed the lowest viability as 1.22 ± 0.20 %. It showed that the crude chloroform extract from Sargassum polycystum C. Agardh is more toxic against breast cancer cell MCF-7. Separation of each crude extract was conducted for further study about bioactivity of Sargassum polycystum C. Agardh and was grouped based on spectrum UV-Vis similarity from 200 – 800 nm. Eight fractions was obtain from each aqueous-metahol and chloroform extract of Sargassum polycystum. Fraction 3 from aqueous-methanol extract (SF3) and fraction 3 from chloroform extract (SK3) has the activity as pro-oxidant and toxic against breast cancer cell with the value of IC50(MTT) 162.21 ± 7.03 ?g/mL for SF3 and 92.69 ± 5.68 ?g/mL for SK3. SK3 also has antibacterial activity against E. coli and S. aureus with clear zone inhibiton diameter 8.67 ± 0.88 mm and 8.33 ± 1.67 mm. Further study on their ability to inhibit DNMT1 showed that SK3 has IC50(DNMT1) value 62.1 ?g/mL while IC50(DNMT1) for SF3 at 153 ?g/mL. This showed that SK3 is 2,47 times higher to inhibit DNMT1 activity than SF3. DNA isolation from breast cancer cell MCF-7 treated with decitabine (1.14 ?g/mL), SF3 (163 ?g/mL) and SK3 (93 ?g/mL) showed fragmentation of DNA. This indicate that treating breast cancer cell MCF-7 with inhibitors DNMT1 could initiate apoptosis in breast cancer cell MCF-7. Identification of compound component of SK3 with GC-MS showed BHT (Buthylated hydroxytoluene), p-cresol and phatalic acid which never been reported as inhibitors for DNMT1 especially from Sargassum polycystum C. Agardh.